Inhibitor compounds of 11-beta-hydroxysteroid dehydrogenase type 1

ABSTRACT

The compounds of formula (I) are derived from perhydroquinoline and perhydroisoquinoline and are useful as active pharmaceutical ingredients for the prophylaxis or treatment of diseases caused by 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) enzyme-associated disorders, such as glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, atherosclerosis, Cushing&#39;s syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer&#39;s disease or neurodegeneration.

This application is a §371 national stage application of PCT International Application No. PCT International Application No. PCT/ES2010/000,258, filed Jun. 4, 2010, claiming priority of Spanish Patent Application No. P200901402, filed Jun. 4, 2009, the contents of all of which are hereby incorporated by reference into this application.

The present invention relates to perhydroquinoline and perhydroisoquinoline derivatives and methods of treating certain diseases using such compounds.

STATE OF THE ART

Glucocorticoids (cortisol in humans, corticosterone in mice and rats) are an important adrenocorticosteroid group regulating many metabolic and homeostatic processes and form a key element of stress response. Glucocorticoids act through the intracellular glucocorticoid receptors and, in some tissues, through mineralocorticoid receptors, both being nuclear transcription factors. The action of glucocorticoids on the target tissues depends not only on circulating steroid concentrations and the cellular expression of the receptors, but also on the intracellular enzymes which critically determine up to what point the glucocorticoids will have active access to the receptors. The 11-beta-hydroxysteroid dehydrogenases (11-beta-HSD) catalyze the interconversion between the main active 11-hydroxy-glucocorticoid (cortisol in man) and its inactive 11-keto metabolites (cortisone in man).

The 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) enzyme reconverts inactive glucocorticoids into active ones, thus playing an important role in modulating cellular agonist concentration and, therefore, in activating corticosteroid receptors in the target tissues. It has been described that the overexpression of 11-beta-HSD1 in mice adipocytes leads to visceral obesity and to the phenotype similar to that of the metabolic syndrome. Collectively, these data significantly confirm the important role of 11-beta-HSD1 in inducing obesity and the disequilibrium of glucose homeostasis and lipid parameters. Therefore, the selective inhibition of this enzyme could reduce the levels of blood glucose in type 2 diabetes patients, normalize the elevated lipid parameters and/or reduce the weight of obese subjects.

The first pharmacological indication that the inhibition of 11-beta-HSD1 in man could have beneficial effects has been achieved by using carbenoxolone, an anti-ulcer drug which inhibits both 11-beta-HSD1 and the similar 11-beta-HSD2 enzyme. Treatment with carbenoxolone increases the sensitivity to insulin, which indicates that the inhibition of 11-beta-HSD1 can reduce the levels of cortisol in the cells and therefore minimize some of its damaging effects.

Studies conducted with the non-specific carbenoxolone inhibitor clearly show the importance of developing 11-beta-HSD1 specific inhibitors. Inhibition of the 11-beta-HSD2 enzyme is poorly tolerated and increases blood pressure. In contrast, inhibition of 11-beta-HSD1 would be well tolerated because it has been observed that the 11-beta-HSD1 knockout mice are healthy and resist hyperglycemia caused by obesity or stress (cf. Kotelevtsev et al., Proc. Natl. Acad. Sci. USA 1997, vol. 94, pp. 14924-14929). Other studies indicate that 11-beta-HSD1 inhibitors can also be beneficial for reducing high blood pressure (cf. Masuzaki et al., J. Clin. Invest. 2003, vol. 112, pp. 83-90), for reducing intraocular pressure (cf. Rauz et al., Q J Med 2003, vol. 96, pp. 481-490), for improving cognitive capacity (cf. Sandeep et al., Proc Natl Acad Sci. USA 2004, vol. 101, pp. 6734-6739) or for improving deficiencies associated with Alzheimer's disease. Overall, inhibition of 11-beta-HSD1 can be a safe and effective strategy for treating symptoms of glaucoma, diabetes, obesity and other diseases.

Glucocorticoids increase the risk of glaucoma by increasing intraocular pressure when they are exogenously administered and in certain conditions of increased production such as Cushing's syndrome. The increase of intraocular pressure induced by corticosteroids is caused by an increased resistance to the aqueous efflux due to changes induced by glucocorticoids.

11-beta-HSD1 is expressed in corneal epithelium basal cells and non-pigmented epithelial cells. The mRNA of the glucocorticoid receptor has been detected in the trabecular reticulum, whereas mRNA for the glucocorticoid receptor, the mineralocorticoid receptor and 1-beta-HSD1 was present in non-pigmented epithelial cells. The administration of carbenoxolone to patients resulted in a significant reduction in intraocular pressure (cf. Rauz et al., Invest. Ophtalmol. Vis. Sci. 2001, vol. 42, pp. 2037-2042), which suggests a role for HSD1 inhibitors in the treatment of glaucoma.

The expression of 11-beta-HSD isoenzymes in human and rodent eyes has been described (cf. Stokes et al., Invest Ophthalmol Vis Sci. 2000, vol. 41, pp. 1629-1638), particularly 11-beta-HSD1 in ciliary epithelial cells, which suggests the possibility of a role in producing aqueous humor and in regulating intraocular pressure. In aqueous humor, cortisol concentrations are approximately 14 times greater than those of cortisone. This suggests to a large extent predominant 11-beta-reductase HSD1 activity. In a double blinded controlled study with glaucoma patients it was observed that treatment with carbenoxolone significantly reduces intraocular pressure therefore 11-beta-HSD1 inhibitors can represent a therapeutic strategy suitable for treating glaucoma.

Document WO2007026920 describes N-arylamide compounds and related compounds as Rho kinase (ROCK) inhibitors, as well as pharmaceutical compositions and the use thereof in treating diseases related to ROCK.

Document WO2006106423 describes N-pyridyl heterocyclylsulfonamide compounds and the use thereof as 11-beta-HSD1 modulators.

Document WO2006048330 describes N-benzylsulfonamide compounds and related derivatives as 11-beta-HSD1 inhibitors, pharmaceutical compositions and the use thereof in therapy.

Document WO2003045367 describes compounds derived from pyridylalkylurea, some of which are structurally similar to those of the present invention but with a different use.

Nevertheless, providing new 11-beta-HSD1 inhibitor compounds is desirable.

DESCRIPTION OF THE INVENTION

The present invention provides new compounds derived from perhydroquinoline and perhydroisoquinoline of formula (I) which are effective as 11-beta-HSD1 inhibitors and have selectivity for 11-beta-HSD1 with respect to 11-beta-HSD2.

Thus, a first aspect of the invention refers to compounds of formula (I)

and pharmaceutically acceptable salts thereof, wherein:

s and p are an integer selected in an opposite manner between 0 and 1, such that when s is 1, p is 0 (to form a perhydroquinoline) and when s is 0, p is 1 (to form a perhydroisoquinoline).

Y is a biradical selected from CO, CS and SO₂,

W1 and W2 can be independently a bond or a biradical selected from O, S and NR1, wherein R1 is optionally H, C₁₋₄ alkyl or C₃₋₁₀ cycloalkyl,

n is an integer selected from 0, 1, 2, 3 and 4,

V is a radical selected from —CO-T, —CS-T and —SO₂-T or a radical selected from:

T is a group selected from NR2R3, R2, OR2 and SR2; or a group selected from

wherein R2 and R3 are independently selected from H, COR4, SO₂R4, C₁₋₄ alkyl, aryl, benzyl, phenethyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₃₋₁₀ cycloalkyl or heterocycle

wherein when R2 or R3 is an alkyl or an alkenyl these can be optionally substituted with one or several substituents independently selected from F, OR4, NR4R5, COOR4, CONR4R5, C₃₋₁₀ cycloalkyl, aryl and heterocycle;

wherein when R2 or R3 is an aryl, a benzyl, a phenethyl, a cycloalkyl or a heterocycle, these can be optionally substituted with one or several substituents independently selected from NH₂, F, Cl, CN, NO₂, COOH, R4, COOR4, OR4, OCF₃, SH, SR4, CONR4R5, SO₂NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO₂R4 and heterocycle,

wherein when R2 or R3 is a cycloalkyl this can be optionally substituted with one or several benzene rings fused with the cycloalkyl, the benzene could be optionally substituted with one or several substituents independently selected from alkyl, alkoxide or halogen,

wherein R4 and R5 are independently selected from H, C₁₋₄ alkyl, aryl, benzyl, phenethyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₃₋₁₀ cycloalkyl and heterocycle

wherein optionally R4 and R5 can be bound to one another forming a 3 to 8 membered cycle.

R6, R7, R8 and R9 are independently selected from H, OR4, F and Cl,

R10 is independently selected from H, OH, F, C₁₋₄ alkyl, COOR11, COR11, phenyl, benzyl, benzhydryl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₃₋₁₀ cycloalkyl and heterocycle, and wherein the alkyl, phenyl, benzyl, benzhydryl, cycloalkyl or heterocycle can be optionally substituted with one or several substituents independently selected from NH₂, F, Cl, NO₂, COOH, COOR4, OR4, CF₃, SH, SR4, CONR4R5, SO₂NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO₂R4 and C₁₋₄ alkyl;

and R11 is selected from H, C₁₋₄ alkyl, aryl and C₃₋₁₀ cycloalkyl.

In a particular embodiment of the invention, s is 0 and p is 1. In another particular embodiment of the invention, s is 1 and p is 0.

In another particular embodiment of the invention, Y is selected from CO and SO₂.

In another particular embodiment of the invention, W1 and W2 are independently selected from a bond, S and NR1. In another particular embodiment of the invention, R1 is H.

In another particular embodiment of the invention, V is selected from —CO-T, —CS-T and —SO₂-T.

In another particular embodiment of the invention, V is selected from

In another particular embodiment of the invention, R2 and R3 are independently selected from H, COR4, SO₂R4, C₁₋₄ alkyl, phenyl, naphthyl, benzyl, phenethyl, C₂₋₄ alkenyl, C₃₋₁₀ cycloalkyl, and heterocycle, particularly, 2-furanyl, 2-thiophenyl, 2-(1-methylindole), quinoline, isoquinoline, 2-benzofuranyl.

In another particular embodiment of the invention, when R2 or R3 are independently C₁₋₄ alkyl or C₂₋₄ alkenyl, R2 or R3 can be optionally substituted with one or several substituents independently selected from F, OR4, NR4R5, COOR4, CONR4R5, phenyl, C₃₋₁₀ cycloalkyl, hexenyl, naphthyl and heterocycle, particularly pyridine, 3-(1-methylindole), 3-thiophenyl and 2-furanyl.

In another particular embodiment of the invention, when R2 or R3 are independently phenyl, benzyl, phenethyl or C₃₋₁₀ cycloalkyl, R2 or R3 can be optionally substituted with one or several substituents independently selected from F, Cl and OR4.

In another particular embodiment of the invention, when R2 or R3 is a cycloalkyl this can be optionally substituted with one or several benzene rings fused with the cycloalkyl, the benzene could be optionally substituted with one or several substituents independently selected from alkyl, alkoxide or halogen.

In another particular embodiment of the invention, R4 and R5 are independently selected from C₁₋₄ alkyl, benzyl, phenethyl and phenyl.

In another particular embodiment of the invention, R4 and R5 can be optionally bound to one another forming a 3 to 8 membered cycle.

In another particular embodiment of the invention, R6, R7, R8 and R9 are independently selected from H, OR4, F and Cl.

In another particular embodiment of the invention, R10 is selected from H, OH, F, C₁₋₄ alkyl, COOR11, COR11, phenyl, benzyl and benzhydryl.

In another particular embodiment of the invention, R10 is selected from phenyl, benzyl and benzhydryl, all of them optionally substituted with one or several substituents, independently selected from F, OR4, CF₃, COR4 and C₁₋₄ alkyl.

In another particular embodiment of the invention, R11 is selected from H and C₃₋₁₀ cycloalkyl.

In another particular embodiment, T is selected from NR2R3, R2, OR2 and SR2.

In another particular embodiment, T is selected from

A second aspect of the present invention refers to a compound of formula (I) or a pharmaceutically acceptable salt thereof for use as a medicament, particularly for the prophylaxis or treatment of diseases caused by 11-beta-HSD1-associated disorders, particularly glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, particularly type II diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease or neurodegeneration, preferably for the prophylaxis or treatment of glaucoma or metabolic syndrome.

Another aspect of the present invention refers to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicaments intended for the prophylaxis or treatment of diseases caused by 11-beta-HSD1-associated disorders, particularly one of the disorders mentioned above.

Another aspect of the present invention refers to a method of prophylaxis or treatment of an individual who is suffering or is susceptible to suffering a disease caused by 11-beta-HSD1-associated disorders, particularly one of the disorders mentioned above, which comprises administrating to said individual a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable excipients.

The compounds of formula (I) and the pharmaceutically acceptable salts thereof, particularly the compounds of formula (I) described as examples or as intermediates are preferred.

The compounds of the present invention can be used alone or in combination with one or more compounds which are useful for the prophylaxis or treatment of diseases such as glaucoma, elevated ocular pressure, metabolic disorders, such as obesity, metabolic syndrome, dyslipidemia, hypertension and/or diabetes, particularly type II diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease and/or neurodegeneration.

The term “C₁₋₄ alkyl”, alone or in combination, means a linear- or branched-chain alkyl group having 1 to 4 carbon atoms.

The terms “C₂₋₄ alkenyl”, and “C₂₋₄ alkynyl”, alone or in combination, mean a linear- or branched chain radical having 2 to 4 carbon atoms and having one or more unsaturated bonds.

The term “C₃₋₁₀ cycloalkyl”, alone or in combination, refers to a stable monocyclic, bicyclic or tricyclic radical of 3 to 10 members, which is saturated or partially saturated, and which only consists of carbon and hydrogen atoms. Examples of C₃₋₁₀ cycloalkyl are the following: cyclopropyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, cycloheptyl, cyclooctyl, 1-tricyclo[3.3.1.1^(3,7)]decanyl, 2-tricyclo[3.3.1.1^(3,7)]decanyl and 2-bicyclo[2.2.1]heptanyl. Unless otherwise specifically established in the specification, the term “cycloalkyl” refers to that including cycloalkyl radicals which are optionally substituted with one or more substituents such as alkyl, halogen, hydroxyl, amino, cyano, nitro, alkoxyl, carboxyl, alkoxycarbonyl, phenyl, etc.

The term “aryl”, alone or in combination refers to radicals of a single ring and multiple rings, including radicals of multiple rings containing separated and/or condensed aryl groups. The typical aryl groups contain 1 to 3 separated or condensed rings and from 6 to 18 carbon ring atoms, such as phenyl or naphthyl radicals, preferably a phenyl group optionally having one or several substituents, preferably from one to three, chosen independently from one another from halogen, trifluoromethyl, trifluoromethoxy, amino, alkyl, alkoxy, alkylcarbonyl, cyano, carbamoyl, alkoxycarbamoyl, methylenedioxy, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxy, nitro, alkyl-SO₂—, amino-SO₂—, cycloalkyl and the like. Phenyl or naphthyl is preferred, particularly phenyl optionally substituted from one to three times, preferably one or two times by substituents chosen independently from one another from alkyl, halogen, alkoxy, trifluoromethoxy, nitro and trifluoromethyl. Phenyl is particularly preferred.

The terms “benzyl” and “phenethyl”, can optionally have one or several substituents, chosen independently from one another from halogen, trifluoromethyl, trifluoromethoxy, amino, alkyl, alkoxy, alkylcarbonyl, cyano, carbamoyl, alkoxycarbamoyl, methylenedioxy, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, hydroxy, nitro, alkyl-SO₂—, amino-SO₂—, cycloalkyl and the like.

The term “heterocycle”, alone or in combination, means a saturated, partially unsaturated or aromatic, 5 to 10 membered heterocycle, containing one or several heteroatoms chosen between nitrogen, oxygen and sulfur. For the purposes of this invention, the heterocycle can be a monocyclic, bicyclic or tricyclic ring system which can include condensed ring systems. The heterocycle can be substituted on one or several carbon atoms e.g. by halogen, alkyl, phenyl, alkoxy, oxo, etc. and/or on a secondary nitrogen atom (i.e., —NH—) by alkyl, cycloalkyl, aralkoxycarbonyl, alcanoyl, phenyl or phenylalkyl or on a tertiary nitrogen atom (i.e., ═N—) by oxide, being especially preferred halogen, alkyl, cycloalkyl and alkoxy. Examples of heterocycle groups are pyrrolidinyl, piperidinyl, piperazinyl, azepine, morpholinyl, thiomorpholinyl, imidazolyl (e.g. imidazol-4-yl and 1-benzyloxycarbonylimidazol-4-yl), pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, hexahydropyrimidinyl, furyl, thienyl, thiazolyl, oxazolyl, indolyl (e.g. 2-indolyl), quinolyl (e.g. 2-quinolyl, 3-quinolyl and 1-oxide-2-quinolyl), isoquinolyl (e.g. 1-isoquinolyl and 3-isoquinolyl), tetrahydroquinolyl (e.g. 1,2,3,4-tetrahydro-2-quinolyl), 1,2,3,4-tetrahydroisoquinolyl (e.g. 1,2,3,4-tetrahydro-1-oxoisoquinolyl)benzimidazoyl, benzothiazoyl and quinoxalinyl. Preferred examples are thiophenyl, quinolyl, piperidyl, morpholyl, thiomorpholyl, oxazolyl, pyridinyl, pyrimidinyl, pyrazolyl, imidazolyl and thiazolyl.

The term “pharmaceutically acceptable salts” means those salts which conserve the efficiency and the biological properties of the free bases or of the free acids and which are not disturbing in a biological sense or in any other sense.

According to the invention, the compounds of formula I and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of diseases caused by 11-beta-HSD1 enzyme-associated disorders.

Unless defined otherwise, all the technical and scientific terms used herein have the same meaning as those commonly understood by a person skilled in the field of the invention. Methods and materials which are similar or equivalent to those described herein can be used in practicing the present invention. Throughout the description and claims the word “comprises” and its variants do not aim to exclude other technical features, additives, components, steps or stereoisomers of the compounds involved. For the persons skilled in the art, other objects, advantages and features of the invention will be inferred partially from the description and partially from practicing the invention.

The compounds of formula (I) can be prepared following different methods known by any person skilled in the field of organic synthesis, particularly through the general processes shown in the following schemes. The starting materials for the preparative methods are commercially available or they can be prepared by means of methods of the literature. All of them started with perhydroquinoline but they are analogous for perhydroisoquinoline.

According to this method an acid-ester (IIa) is treated with decahydroquinoline in the presence of a suitable coupling agent, such as for example the combination of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and 1-hydroxybenzotriazole (HOST), or by means of converting the acid to the corresponding acyl halide with a large variety of reagents such as thionyl chloride, sulfuryl chloride, oxalyl chloride, etc. In the presence of a tertiary base such as Et₃N (Elmore, Amino Acids Pep. Proteins 2001, vol. 32, pp. 107-162) for obtaining the amide-ester intermediate (IIIa). The diamide (Ia) is obtained by means of a prior saponification of the compound (IIIa) in aqueous medium with bases of the LiOH type, NaOH type, etc. and subsequent formation of the diamide with any of the methods previously described for the intermediate (IIIa).

Scheme 2 shows the reaction of the decahydroquinoline with diphosgene or triphosgene and subsequent addition of amino-ester, hydroxy-ester or mercapto-ester type derivatives respectively providing the urea-ester, carbamate-ester or thiocarbamate-ester type intermediates. Subsequently a deprotection and coupling treatment similar to that described in scheme 1 for obtaining the amide derivatives is performed.

Scheme 3 shows a method for preparing the compounds amido-succinimide (Ic and Ik), amido-amide (Id), amido-sulfonamide (It) and amido-urea or amido-thiourea (Ie) of the present invention. The intermediate amine (Vc) can be prepared by means of two alternative methods: on one hand Gabriel synthesis with potassium phthalimide from the intermediate (IIIc) providing the compound (Ic) and subsequent treatment of this compound with hydrazine under EtOH reflux yielding the mentioned amine (Vc), optionally the intermediate (IIIc) is reacted with sodium azide generating alkyl azide (IVc) which provides the amine (Vc) by reduction.

The intermediate amine (Vc) can be converted both into amide (Id) and into sulfamide (It) by any of the methods previously described or into urea or thiourea (Ie) by means of reaction with an isocyanate or thioisocyanate, respectively. The compound of formula (Ik) can easily be prepared by condensing an anhydride of a 1,2-dicarboxylic acid of general formula (IIc) and the intermediate amine (Vc) previously described.

Scheme 4 shows a method for preparing the compounds of the present invention applying a combination of methods previously described in the schemes above to provide ureas and thioureas from decahydroquinoline with different terminal functionalities already described previously in scheme 3.

Scheme 5 shows a method for preparing the compounds of the present invention of amido-carbamate and amido-O-thiocarbamate type. The reduction of the intermediate ester (IIIa) to alcohol (IVj) by means of saponification of the ester, formation of a mixed anhydride and subsequent reduction thereof with sodium borohydride. The reaction of the alcohol (IVj) with isocyanate, thiocyanate, carbamoyl chloride or thiocarbamoyl chloride provides the carbamate or O-thiocarbamate (Ij).

Scheme 6 shows a method for preparing the compounds of the present invention of amido-S-thiocarbamate and amido-dithiocarbamate type. After the formation of the intermediate amide (IVp) by methods previously described and its subsequent reaction with isocyanate, thiocyanate, carbamoyl chloride or thiocarbamoyl chloride provides S-thiocarbamate or dithiocarbamate (Ip).

Scheme 7 shows a method for preparing the sulfonamide (Im) in which decahydroquinoline is reacted with the sulfonyl ester chloride (IIm). The deprotection and coupling treatment previously described in scheme 1 provides the sulfonamides (Im),

EXAMPLES

The following examples serve to better illustrate the invention but they must not be considered as limiting the same.

The nomenclature used in the present document is based on the Beilstein-Institut computer program known as AUTONOM (Automatic Nomenclature), which uses the systematic nomenclature of the IUPAC

Abbreviations:

-   AcOEt ethyl acetate -   Brine saturated NaCl solution -   DCM dichloromethane -   DMF dimethylformamide -   DMSO dimethylsulfoxide -   EDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide -   Et₃N triethylamine -   EtOH ethanol -   HOBT 1-hydroxybenzotriazole -   HPLC High performance liquid chromatography -   MeOH methanol -   MS Mass spectrometry -   m/z Mass/charge ratio -   rt Room temperature -   THF tetrahydrofuran -   TLC Thin layer chromatography -   tr Retention time -   UV Ultraviolet     General Data:

The products were analyzed using Agilent HPLC-UV-MS equipment provided with a UV detector of variable wavelength and a mass spectrometer model 1100 VL. The wavelength used for detecting UV was 210 nm, whereas the MS detector has been operated in a positive electrospray ionization mode and a 100 to 700 m/z scan has been performed. Concerning chromatographic separation, the column used was a Kromasil 100 C18, 40×4.0 mm, 3.5 μm, and 2-5 μl have been injected. For the elution one of the two solvent gradients described below was followed:

Method A: 5-90% B, 0-8 min; 90% B, 8-11 min; 5% B, 9-11 min. The flow rate of the mobile phase is 0.7 ml/min.

Method B: 5-90% B, 0-4.5 min; 90% B, 45-6 min; 5% B, 6-7 min. The flow rate of the mobile phase is 1.4 ml/min.

In both cases, the solvent A consists of 0.2% formic acid in water, whereas B is 0.2% formic acid in acetonitrile.

Alternatively, the analysis was conducted by means of Waters HPLC-UV-MS equipment provided with a detector having diodes in series and a mass spectrometer model EMDI000. The wavelength used for detecting UV was 210 nm, whereas the MS detector has been operated in a positive electrospray ionization mode and a 100 to 700 m/z scan has been performed. Concerning chromatographic separation, the column used was a Kromasil C18 2.1×50 mm, 3.5 μm and 2 μl have been injected. For the elution, the following gradient was followed:

The flow rate of the mobile phase is 0.5 ml/min.

Intermediate IIIa.1 ethyl 3-(octahydroquinolin-1-yl)-3-oxopropionate

3.38 mL of Et₃N and 1.44 mL (11 mmol) of ethyl 3-chloro-3-oxopropionate are added to a solution of 1.5 mL (10 mmol) of decahydroquinoline in 100 mL of AcOEt. The resulting solution is kept under stirring at reflux for 10 h. Then water is added and the organic phase is separated, the aqueous phase is extracted once again with AcOEt. The organic phases are pooled and they are first washed with 5% solution of NaHCO₃ and subsequently with brine, they are dried over anhydrous

Na₂SO₄, they are filtered and the solvent is evaporated under reduced pressure. 2.0 g of a yellow oil are obtained. It is identified as intermediate IIIa.1. Method A: tr: 6.76 min; m/z: 268.

Intermediate IIIa.2 6-(octahydroisoquinolin-2-yl)-6-oxohexanoic acid methyl ester

80 mL of AcOEt and, then, 3 mL (22 mmol) of Et₃N are added to a mixture formed by 1.1 mL (8.32 mmol) of decahydroisoquinoline, 1.5 mL (10 mmol) of monomethyl adipate, 2 g (15 mmol) of HOBT and 2.9 g (15 mmol) of EDC. The solution formed is kept under stirring for 18 h. Then, it is treated with water and AcOEt, the organic phase is separated and the aqueous phase is extracted once more with AcOEt. The organic phases are pooled and they are washed successively with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. 1.5 g of an oil identified as intermediate IIIa.2 are obtained.

Method B: tr: 3.66 min/3.78 min; m/z: 282/282

The following intermediates were prepared in a manner similar to intermediates IIIa.1 or IIIa.2:

Int. structure name method tr (min) m/z IIIa.3

(Octahydroquinolin-1-yl)oxoacetic acid ethyl ester A 6.83 240 IIIa.4

3-(octahydroquinolin-1-yl)-3- oxopropionic acid ethyl ester A 6.37 254 IIIa.5

5-(octahydroquinolin-1-yl)-5- oxopentanoic acid ethyl ester A 6.96 282 IIIa.6

(Octahydroisoquinolin-2-yl)oxoacetic acid ethyl ester A 6.83 7.05 240 240 IIIa.7

3-(octahydroisoquinolin-2-yl)-3- oxopropionic acid methyl ester A 5.86 6.09 240 240 IIIa.8

4-(octahydroisoquinolin-2-yl)-4- oxobutyric acid ethyl ester A 6.72 6.92 268 268 IIIa.9

5-(octahydroisoquinolin-2-yl)-5- oxopentanoic acid ethyl ester A 7.13 7.55 282 282 IIIa.10

6-(octahydroquinolin-1-yl)-6- oxohexanoic acid methyl ester B 3.67 282

Intermediate IIIb.1 3-[(octahydroquinoline-1-carbonyl)amino]propionic acid methyl ester

Step 1:

2.5 g (18 mmol) of decahydroquinoline are dissolved in 150 mL of DCM and 2.7 g (9 mmol) of triphosgene are slowly added to the solution formed, preventing the temperature from exceeding 25° C. The resulting mixture is then refluxed for 18 h. It is then evaporated to dryness and the residue obtained is purified by means of silica gel filtration using AcOEt as eluent, obtaining 2 g of a yellowish oil identified as 1-chlorocarbonyloctahydroquinoline.

IR: 1729.

Step 2:

0.5 g (3.5 mmol) of the 3-aminopropionic acid methyl ester hydrochloride are dissolved in 5 mL of anhydrous THF and 0.9 mL of Et₃N. Once dissolved, 650 mg of 1-chlorocarbonyloctahydroquinoline are slowly added and it is refluxed for 18 h. AcOEt is then added and the resulting solution is sequentially washed with water, 1N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure yielding 580 mg of intermediate IIIb.1.

Method B: tr: 3.17 min; m/z: 269.

The following intermediates were prepared in a manner similar to intermediate IIIb.1:

Int. structure name method tr (min) m/z IIIb.2

4-[(octahydroquinoline-1- carbonyl)amino]butyric acid methyl ester B 3.29 283 IIIb.3

3-(octahydroisoquinoline-2- carbonyl)amino]propionic acid methyl ester B 3.29 269 IIIb.4

4-[(octahydroisoquinoline-2- carbonyl)amino]butyric acid methyl ester B 3.40 283

Intermediate IIIb.5 3-(octahydroisoquinoline-2-carbonylsulfenyl)propionic acid methyl ester

Step 1:

2-chlorocarbonyloctahydroisoquinoline: it was prepared in a manner similar to that described for step 1 of intermediate IIIb.1. IR: 1737.

Step 2:

1 g (5 mmol) of 2-chlorocarbonyloctahydroisoquinoline is added to a 0° C. solution of 0.55 mL (5 mmol) of 3-mercaptopropionic acid methyl ester in 10 mL of pyridine. Once added, it is left under stirring at rt for 18 h. AcOEt is then added to the reaction mixture and it is sequentially washed with a 5% solution of NaHCO₃, 1N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure being purified by means of silica gel column chromatography, using a (1:1) mixture of hexane:AcOEt as eluent, yielding 1.17 g of a residue identified as intermediate IIIb.5. and 210 mg of a solid identified as his-(octahydroisoquinolin-2-yl)methanone (Vb.1)

Method B: for IIIb.5 tr: 4.35 min; m/z: 286.

-   -   for Vb.1: tr: 5.34 min; m/z: 305,

The following intermediates were prepared in a manner similar to intermediate IIIb.5:

Int. structure name method tr (min) m/z IIIb.6

3-(octahydroquinoline-1- carbonylsulfenyl)propionic acid methyl ester B 4.23 286 IIIb.7

4-(octahydroquinoline-1- carbonylsulfenyl)butyric acid benzyl ester B 5.04 376 IIIb.8

4-(octahydroisoquinoline-2- carbonylsulfenyl)butyric acid benzyl ester B 5.14 377

Intermediate IIIm.1 3-(octahydroquinoline-1-sulfonyl)propionic acid methyl ester

Step 1

4.48 mL (55.9 mmol) of sulfuryl chloride are added dropwise to a mixture formed by 2.47 mL (22.4 mmol) of methyl 3-mercaptopropionate and 5.64 g (55.9 mmol) of potassium nitrate cooled to 0° C. Once added it is left to reach rt keeping the stirring for 10 h. Saturated NaHCO₃ solution is added and the organic phase is separated, which is subsequently washed again with NaHCO₃ and then with brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure yielding 2.6 g of an oil identified as the 3-chlorosulfonylpropionic acid methyl ester.

Method B: tr: 2.05 min; m/z: non ionizable.

Step 2

2.1 mL of Et₃N (15.3 mmol) and subsequently, dropwise, 1.3 g (7 mmol) of the 3-chlorosulfonylpropionic acid methyl ester are added to a solution formed by 1.1 mL (7.6 mmol) of decahydroquinoline in 70 mL of AcOEt. The mixture is heated to 70° C. and that temperature is maintained for 12 h. It is then left to cool and water is added, the organic phase is separated and it is sequentially washed with 5% solution of sodium bicarbonate, 2N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure yielding 1.32 g of a reddish oil identified as intermediate IIIm.1.

Method B: tr: 3.36 min: m/z: 290

The following intermediates were prepared in a manner similar to intermediate IIIm.1:

Int. structure name method tr (min) m/z IIIm.2

4-(octahydroquinoline-1- sulfonyl)butyric acid methyl ester B 3.73 304 IIIm.3

3-(octahydroisoquinoline-2- sulfonyl)propionic acid methyl ester B 3.79 290 IIIm.4

4-(octahydroisoquinoline-2- sulfonyl)butyric acid methyl ester B 3.83 3.91 304 304

Intermediate IVb.1 4-[(octahydroisoquinoline-2-carbonyl)amino]butyric acid

1.2 g (4.21 mmol) of intermediate IIIb.4 are dissolved in a mixture formed by 37.5 mL of THF and 12.5 mL of MeOH, and 5.1 mL of a 1M LiOH solution in water are added to the solution formed. The resulting mixture is kept under stirring at rt for 18 h. Then it is diluted in AcOEt and washed with water, the aqueous phase is acidified with a 1N solution of HCl until pH=3 and it is extracted with AcOEt. Finally, the organic phases are pooled, they are dried over anhydrous Na₂SO₄, they are filtered and the solvent is evaporated under reduced pressure. 570 mg of a white solid are obtained.

Method B: tr: 2.85 min/2.96 min; m/z: 269/269

The following intermediates were prepared in a manner similar to intermediate IVb.1:

Int. structure name method tr (min) m/z IVa.1

3-(octahydroquinolin-1-yl)-3- oxopropionic acid A 5.18 226 IVa.2

4-(octahydroquinolin-1-yl)-4- oxobutyric acid A 5.32 240 IVa.3

5-(octahydroquinolin-1-yl)-5- oxopentanoic acid A 5.42 254 IVa.4

6-(octahydroisoquinolin-2-yl)-6- oxobutyric acid B 3.08 268 IVa.5

(octahydroisoquinolin-2- yl)oxoacetic acid A 4.25 4.40 212 212 IVa.6

3-(octahydroisoquinolin-2-yl)-3- oxopropionic acid A 5.19 5.40 226 226 IVa.7

4-(octahydroisoquinolin-2-yl)-4- oxobutyric acid A 5.30 5.51 240 240 IVa.8

5-(octahydroisoquinolin-2-yl)-5- oxopentanoic acid A 5.44 5.64 254 254 IVa.9

6-(octahydroisoquinolin-2-yl)-6- oxohexanoic acid B 3.09 3.20 268 268 IVb.2

3-[(octahydroquinoline-1- carbonyl)amino]propionic acid B 2.75 255 IVb.3

4-[(octahydroquinoline-1- arbonyl)amino]butyric acid B 2.85 269 IVb.4

3-[(octahydroisoquinoline-2- carbonyl)amino]propionic acid B 2.87 255 IVb.5

3-(octahydroquinoline-1- carbonylsulfenyl)propionic acid B 3.53 272 IVb.6

3-(octahydroisoquinoline-2- carbonylsulfenyl)propionic acid B 3.66 272 IVb.7

4-(octahydroisoquinoline-2- carbonylsulfenyl)butyric acid B 3.81 286 IVm.1

3-(octahydroquinoline-1- sulfonyl)propionic acid B 3.10 276 IVm.2

4-(octahydroquinoline-1- sulfonyl)butyric acid B 3.18 290 IVm.3

3-(octahydroisoquinoline-2- sulfonyl)propionic acid B 3.18 3.27 276 276 IVm.4

4-(octahydroisoquinoline-2- sulfonyl)butyric acid B 3.25 3.34 290 290

Intermediate IIIc.1 4-bromo-1-(octahydroquinolin-1-yl)butan-1-one

1.37 mL (9.9 mmol) of Et₃N and 0.5 mL (4.5 mmol) of 5-bromovaleric acid chloride are added to a solution of 1 mL (4.0 mmol) of the decahydroquinoline in AcOEt. The resulting solution is kept under stirring for 18 h at rt. The solution is then washed with water, and the water re-extracted twice with AcOEt. The pooled organic phases are sequentially washed with 5% solution of NaHCO₃, 1N HCl and saturated ammonium chloride solution. Finally the organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. 1.2 g of a yellow oil, which was used without subsequent purification, are obtained.

The following intermediates were prepared in a manner similar to intermediate IIIc.1:

Int. structure name method tr (min) m/z IIIc.2

2-chloro-1-(octahydroquinolin- 1-yl)ethanone A 6.45 216, 218  IIIc.3

3-chloro-1-(octahydroquinolin- 1-yl)propan-1-one A 7.02 230, 232  IIIc.4

5-bromo-1- (octahydroisoquinolin-2- yl)-pentan-1-one A 7.60 7.78 (302, 304) (302, 304) IIIc.5

2-chloro-1- (octahydroisoquinolin-2- yl)ethanone A 6.44 6.68 (216, 218) (216, 218) IIIc.6

3-bromo-1- (octahydroisoquinolin-2- yl)propan-1-one A 7.00 7.21 (274, 276) (274, 276) IIIc.7

5-bromo-1-(octahydroquinolin- 1-yl)-pentan-1-one A — —

Intermediate IIIf.1 Octahydroquinoline-1-carboxylic acid 3-chloropropylamide

2.5 g (21 mmol) of 3-chloropropylisocyanate are dissolved in 150 mL of anhydrous THF and 6.4 mL (46 mmol) of Et₃N. Once dissolved 3.4 mL (23 mmol) of decahydroquinoline are slowly added and it is refluxed for 18 h. AcOEt is then added and the resulting solution is sequentially washed with water, 1N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure yielding 4.6 g of intermediate IIIf.1. Method B: tr: 3.58 min; m/z: 259

Intermediate IIIf.2 Octahydroisoquinoline-2-carboxylic acid 3-(chloropropyl)amide

It was prepared in a manner similar to that described for intermediate IIIf.1. Method B: tr: 357 min/3.68 min; m/z: 259, 259

Intermediate IVc.1 4-azido-1-(octahydroquinolin-1-yl)butan-1-one

710 mg (10.8 mmol) of sodium azide are added to a solution of 1.1 g (3.6 mmol) of intermediate IIIc.1 in 35 mL of anhydrous DMF. The resulting solution is kept under stirring for 18 h at a temperature of 90° C. The solution is then cooled and water is added, extracting three times with AcOEt. The pooled organic phases are washed with brine. Finally the organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. 830 mg of a yellow oil, which was used without subsequent purification, are obtained. Method A: tr: 7.07 min; m/z: 251.

The following intermediates were prepared in a manner similar to intermediate IVc.1:

Int. structure name method tr (min) m/z IVc.2

2-azido-1-(octahydroquinolin- 1-yl)ethanone A 6.48 223 IVc.3

3-azido-1-(octahydroquinon- 1-yl)propan-1-one A 6.79 237 IVc.4

5-azido-1-(octahydroquinolin- 1-yl)pentan-1-one A 7.33 265 IVc.5

2-azido-1- (octahydroisoquinolin-2- yl)ethanone A 6.46 6.70 223 223 IVc.6

3-azido-1- (octahydroisoquinolin-2- yl)propan-1-one A 6.77 6.99 237 237 IVc.7

4-azido-1- (octahydroisoquinolin-2- yl)butan-1-one A 7.07 7.27 251 251 IVc.8

5-azido-1- (octahydroisoquinolin-2- yl)pentan-1-one A 7.33 7.51 265 265 IVf.1

Octahydroquinoline-1- carboxylic acid (3- azidopropyl)amide B 3.56 266 IVf.2

Octahydroisoquinoline-2- carboxylic acid (3- azidopropyl)amide B 3.55 3.66 266 266

Intermediate Ic.1 2-[4-(octahydroquinolin-1-yl)-4-oxobutyl]isoindole-1,3-dione

200 mg (1.1 mmol) of potassium phthalimide are added to a solution of 307 mg (1.1 mmol) of intermediate IIIc.1 in 10 mL of anhydrous DMF. The resulting solution is kept under stirring for 18 h at a temperature of 90° C. The solution is then cooled and water is added, extracting it with AcOEt. The pooled organic phases are washed with brine. Finally the organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. 360 mg of a paste, which was purified by means of silica gel column chromatography using a (1:1) mixture of hexane:AcOEt as eluent, yielding 180 mg of an oil identified as intermediate Ic.1, are obtained. Method A: tr: 7.17 min; m/z: 355.

The following intermediates were prepared in a manner similar to intermediate Ic.1:

Ex. structure name method tr (min) m/z Ic.2

2-[2-(octahydroquinolin-1-yl)- 2-oxoethyl]isoindole-1,3-dione A 6.93 327 Ic.3

2-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]isoindole-1,3-dione A 7.00 341 Ic.4

2-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]isoindole-1,3-dione A 7.17 355 Ic.5

2-[2-(octahydroisoquinolin-2- yl)-2-oxoethyl]isoindole-1,3- dione A 6.92 7.10 327 327 Ic.6

2-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]isoindole-1,3- dione A 6.96 7.12 341 341 Ic.7

2-[4-(octahydroisoquinolin-2- yl)-4-oxobutyl]isoindole-1,3- dione A 7.16 7.33 355 355 Ic.8

2-[5-(octahydroisoquinolin-2- yl)-5-oxopentyl]isoindole-1,3- dione A 7.39 7.55 369 369

Intermediate Vc.1 4-amino-1-(octahydroquinolin-1-yl)butan-1-one

-   -   Option A: 0.1 mL of hydrazine (2.5 mmol) is added to a solution         formed by 172 mg (0.48 mmol) of intermediate Ic.1 in 5 mL of         EtOH and it is heated to reflux temperature for 2 h. The         solution is then cooled and concentrated HCl is added until         acidic pH is reached, stirring it for 2 h or more. The resulting         suspension is filtered and the water is basified with 1N NaOH,         extracting it with DCM. The pooled organic phases are washed         with brine and are dried over anhydrous Na₂SO₄, it is filtered         and the solvent is evaporated under reduced pressure. The         resulting residue is purified by means of silica gel column         chromatography, using a (10:1) mixture of DCM:MeOH as eluent,         yielding 90 mg of an oil identified as intermediate Vc.1.     -   Option B: A suspension formed by 830 mg (3.32 mmol) of         intermediate IVc.1 and 83 mg of 5% Pd/C in 35 mL of MeOH is         stirred under hydrogen atmosphere until the disappearance of the         starting product by monitoring by TLC. It is filtered through         Celite and it is evaporated to dryness yielding 700 mg of an oil         identified as intermediate Vc.1.

Method A: tr: 3.94 min; m/z: 225

The following intermediates were prepared in a manner similar to intermediate Vc.1:

Int. structure name method tr (min) m/z Vc.2

2-amino-1-(octahydroquinolin- 1-yl)ethanone A 3.41 197 Vc.3

3-amino-1-(octahydroquinolin- 1-yl)propan-1-one A 3.64 211 Vc.4

5-amino-1-(octahydroquinolin- 1-yl)pentan-1-one A 4.01 239 Vc.5

2-amino-1- (octahydroisoquinolin-2- yl)ethanone A 3.69 197 Vc.6

3-amino-1- (octahydroisoquinolin-2- yl)propan-1-one A 4.00 211 Vc.7

4-amino-1- (octahydroisoquinolin-2- yl)butan-1-one A 4.03 225 Vc.8

5-amino-1- (octahydroisoquinolin-2- yl)pentan-1-one A 4.27 239 Vc.9

Octahydroquinoline-1- carboxylic acid (3- aminopropyl)amide B 2.11 240 Vc.10

Octahydroisoquinoline-2- carboxylic acid (3- aminopropyl)amide B 2.22 240

Intermediate IVj.1 5-hydroxyl-1-(octahydroisoquinolin-2-yl)pentan-1-one

0.63 mL (4.93 mmol) of isobutyl chloroformate are added dropwise to a solution of 1.25 g (4.93 mmol) of intermediate IVa.8 and 0.6 mL of N-methylmorpholine (5.4 mmol) in 50 mL of anhydrous THF and cooled to 0° C. The resulting solution is left to stir for 30 minutes at that temperature and 370 mg (9.86 mmol) of sodium borohydride are then added. Once added it is left to reach rt and it is stirred for 2 h. It is then partitioned between AcOEt and water. The aqueous phase is extracted twice with AcOEt, the organic phases are pooled, dried over anhydrous Na₂SO₄, filtered and evaporated to dryness, 1 g of a yellow oil, which was used without subsequent purification, being obtained.

Method B: tr: 2.94 min/3.06 min; m/z: 240/240.

Intermediate IVj.2 5-hydroxyl-1-(octahydroquinolin-1-yl)pentan-1-one

It is prepared in a manner similar to that described for intermediate IVj.1. Method B: tr: 2.94 min; mfz: 240

Intermediate IVp.1 3-mercapto-1-(octahydroquinolin-1-yl)propan-1-one

8.5 mL of Et₃N, 6.5 g of EDC (mmol) and 5.7 g of HOBT (mmol) are added to a solution formed by 3 g (28.2 mmol) of 3-mercaptopropionic acid in 45 mL of DMF and cooled to 0° C. and it is left for 15 minutes under stirring at that temperature. 4.2 g (28.3 mmol) of decahydroquinoline are then added and it is stirred at rt for 18 h. Then, it is treated with water and AcOEt, the organic phase is separated and the aqueous phase is extracted once more with AcOEt. The organic phases are pooled and successively washed with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The resulting residue is purified by means of silica gel column chromatography, using a (50:1) mixture of DCM:MeOH as eluent, yielding 600 mg of the thiol intermediate

Intermediate IVp.2 3-mercapto-1-(octahydroisoquinolin-2-yl)propan-1-one

It is prepared in a manner similar to that described for intermediate IVp.1, Method B: tr: 3.59 min/3.72 min; m/z: 228/228

Intermediate IVp.3 4-mercapto-1-(octahydroquinolin-1-yl)butan-1-one

1.5 mL of decahydroquinoline (10 mmol) and 10 mg of camphorsulfonic acid are added to a solution formed by 0.9 mL (10 mmol) of γ-thiolactone in 80 mL of toluene. The resulting mixture is left to stir at 100° C. for 6 h. The solvent is then evaporated under reduced pressure and the resulting residue is purified by means of silica gel column chromatography, using a (50:1) mixture of DCM:MeOH as eluent, yielding 1.5 g of the thiol intermediate IVp.3. Method B: tr: 3.75 min; m/z: 242

Intermediate IVp.4 4-mercapto-1-(octahydroisoquinolin-2-yl)butan-1-one

It is prepared in a manner similar to that described for intermediate IVp.3. Method B: tr: 3.75 min/3.87 min; m/z: 242/242

Example Ia.1 N-bicyclo[2.2.1]hept-2-yl-3-(octahydroisoquinolin-2-yl)-3-oxopropionamide

43 μL (0.31 mmol) of Et₃N, 29 mg (0.21 mmol) of HOBT, 41 mg (0.21 mmol) of EDC and 18.6 μL (0.16 mmol) of 2-aminonorbornan are added to a solution of 32 mg (0.14 mmol) of the acid intermediate IVa.6 in 2 mL of AcOEt. The solution formed is kept under stirring for 18 h. It is then treated with water and more AcOEt is added, the organic phase is separated and the aqueous phase is extracted once more with more AcOEt. The organic phases are pooled and successively washed with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. 27 mg of the compound identified as example Ia.1 are obtained. Method A: tr: 6.76 min/6.84 min; m/z: 319/319

The following examples were prepared in a manner similar to example Ia.1:

Ex. structure name method tr (min) m/z Ia.2

1-(3,5-dimethylpiperidin-1 yl)-2-(octahydroquinolin-1- yl)ethane-1,2-dione A 7.22 7.35 307 307 Ia.3

1-(6,7-dimethoxy-3,4- dihydro-1-H-isoquinolin-2- yl)-2-(octahydroquinolin-1- yl)ethane-1,2-dione A 6.54 387 Ia.4

1,2-bis-(octahydroquinolin- 1-yl)ethane-1,2-dione A 7.66 7.76 333 333 Ia.5

1-(octahydroquinolin-1-yl)- 2-(piperidin-1-yl)ethane- 1,2-dione A 6.19 279 Ia.6

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 2-(octahydroquinolin-1- yl)ethane-1,2-dione A 6.19 309 Ia.7

1-(octahydroquinolin-1-yl)- 2-(4-oxopiperidin-1- yl)ethane-1,2-dione A 5.10 293 Ia.8

1-(4-methylpiperazin-1-yl)- 2-(octahydroquinolin-1- yl)ethane-1,2-dione A 3.82 294 Ia.9

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-2-(octahydroquinolin- 1-yl)ethane-1,2-dione A 7.00 386 Ia.10

1-(octahydroquinolin-1-yl)- 2-[4-(3- trifluoromethylphenyl) piperazin-1-yl]-ethane-1,2- dione A 7.90 424 Ia.11

1-(octahydroquinolin-1-yl)- 2-(4-o-tolylpiperazin-1- yl)ethane-1,2-dione A 7.82 370 Ia.12

2-(octahydroquinolin-1-yl)- 2-oxo-N- tricyclo[3.3.1.1^(3.7)]decan-2- ylacetamide A 7.99 8.18 345 345 Ia.13

1-(octahydroisoquinolin-2- yl)-2-(octahydroquinolin-1- yl)ethane-1,2-dione A 7.69 7.84 333 333 Ia.14

N-(bicyclo[2.2.1]hept-2- yl)-2-(octahydroquinolin-1- yl)-2-oxoacetamide A 6.98 7.13 305 305 Ia.15

2-(octahydroquinolin-1-yl)- 2-oxo-N- tricyclo[3.3.1.1^(3,7)]decan-1- ylacetamide A 8.15 8.33 345 345 Ia.16

1-(octahydroquinolin-1-yl)- 3-(piperidin-1-yl)propane- 1,3-dione A 6.09 293 Ia.17

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-3-(octahydroquinolin- 1-yl)propane-1,3-dione A 6.46 400 Ia.18

1-(3,5-dimethylpiperidin-1- yl)-3-(octahydroquinolin-1- yl)propane-1,3-dione A 7.03 7.17 321 321 Ia.19

1-(4-methylpiperidin-1-yl)- 3-(octahydroquinolin-1- yl)propane-1,3-dione A 6.62 307 Ia.20

1-(3-methylpiperidin-1-yl)- 3-(octahydroquinolin-1- yl)propane-1,3-dione A 6.62 307 Ia.21

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 3-(octahydroquinolin-1- yl)propane-1,3-dione A 5.90 323 Ia.22

1,3-bis-(octahydroquinolin- 1-yl)propane-1,3-dione A 7.53 347 Ia.23

1-(octahydroquinolin-1-yl)- 3-(4-o-tolylpiperazin-1- yl)propane-1,3-dione A 7.56 384 Ia.24

1-(4-benzylpiperidin-1-yl)- 3-(octahydroquinolin-1- yl)propane-1,3-dione A 6.31 460 Ia.25

1-(4-benzhydrylpiperazin- 1-yl)-3-(octahydroquinolin- 1-yl)propane-1,3-dione A 7.72 383 Ia.26

N-bicyclo[2.2.1]hept-2-yl- 3-(octahydroquinolin-1-yl)- 3-oxopropionamide A 6.76 6.84 319 319 Ia.27

1-(octahydroisoquinolin-2- yl)-3-(octahydroquinolin-1- yl)propane-1,3-dione A 7.54 7.68 347 347 Ia.28

1-(4-methylpiperazin-1-yl)- 3-(octahydroquinolin-1- yl)propane-1,3-dione A 3.90 308 Ia.29

1-(octahydroisoquinolin-2- yl)-4-(octahydroquinolin-1- yl)butane-1,4-dione A 7.75 7.90 361 361 Ia.30

1,4-bis-(octahydroquinolin- 1-yl)butane-1,4-dione A 7.84 361 Ia.31

1-(octahydroquinolin-1-yl)- 4-(4-o-tolylpiperazin-1- yl)butane-1,4-dione A 7.78 398 Ia.32

1-(4-benzylpiperidin-1-yl)- 4-(octahydroquinolin-1- yl)butane-1,4-dione A 7.99 8.11 397 397 Ia.33

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-4-(octahydroquinolin- 1-yl)butane-1,4-dione A 6.53 414 Ia.34

1-(3,5-dimethylpiperidin-1- yl)-4-(octahydroquinolin-1- yl)butane-1,4-dione A 7.32 7.48 335 335 Ia.35

1-(4-methylpiperidin-1-yl)- 4-(octahydroquinolin-1- yl)butane-1,4-dione A 6.93 321 Ia.36

1-(3-methylpiperidin-1-yl)- 4-(octahydroquinolin-1- yl)butane-1,4-dione A 6.92 321 Ia.37

1-(octahydroquinolin-1-yl)- 4-piperidin-1-ylbutane-1,4- dione A 6.36 307 Ia.38

1-(octahydroquinolin-1-yl)- 4-(6-oxooctahydroindol-1- yl)butane-1,4-dione A 4.25 361 Ia.39

1-(4-methylpiperazin-1-yl)- 4-(octahydroquinolin-1- yl)butane-1,4-dione A 4.19 322 Ia.40

N-bicyclo[2.2.1]hept-2-yl- 4-(octahydroquinolin-1-yl)- 4-oxobutyramide A 6.84 333 Ia.41

1-(3-methylpiperidin-1-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione A 7.01 335 Ia.42

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione A 6.28 351 Ia.43

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid bicyclo[2.2.1]hept-2-ylamide A 6.88 347 Ia.44

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-5-(octahydroquinolin- 1-yl)pentane-1,5-dione A 6.75 428 Ia.45

1-(3,5-dimethylpiperidin-1- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione A 7.41 7.57 349 349 Ia.46

1,5-bis-(octahydroquinolin- 1-yl)pentane-1,5-dione A 7.92 375 Ia.47

1-(octahydroisoquinolin-2- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione A 7.91 8.08 375 375 Ia.48

1-(octahydroquinolin-1-yl)- 5-(4-o-tolylpiperazin-1- yl)pentane-1,5-dione A 7.89 412 Ia.49

1-(4-benzylpiperidin-1-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione A 8.05 411 Ia.50

1-(4-benzhydrylpiperazin- 1-yl)-5-(octahydroquinolin- 1-yl)pentane-1,5-dione A 6.54 488 Ia.51

1-(3,4-dihydro-2-H- quinolin-1-yl)-5- (octahydroquinolin-1- yl)pentane-1,5-dione A 7.49 369 Ia.52

1-(octahydroquinolin-1-yl)- 5-(1-oxo-3,4-dihydro-1-H- isoquinolin-2-yl)pentane- 1,5-dione A 7.75 383 Ia.53

1-(6,7-dimethoxy-3,4- dihydro-1-H-isoquinolin-2- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione A 6.58 429 Ia.54

1-(octahydroquinolin-1-yl)- 5-(6-oxooctahydroindol-1- yl)pentane-1,5-dione A 4.30 375 Ia.55

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid cyclohexylamide B 3.68 335 Ia.56

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid (3- phenylpropyl)amide B 3.84 371 Ia.57

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid (pyridin-3-ylmethyl)amide B 2.29 344 Ia.58

1-(4-benzylpiperazin-1-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione B 2.63 412 Ia.59

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid phenethylamide B 3.66 357 Ia.60

1-(4-hydroxypiperidin-1- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione B 2.75 337 Ia.61

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid benzylamide B 3.54 343 Ia.62

1-(3-hydroxypiperidin-1- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione B 2.87 337 Ia.63

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid ethylmethylamide B 3.24 295 Ia.64

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid methylpropylamide B 3.51 309 Ia.65

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid butylmethylamide B 3.79 323 Ia.66

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid methylnaphthalen-1- ylmethylamide B 4.24 407 Ia.67

5-(octahydroquinolin-1-yl)- 1-perhydroazepin-1- ylpentane-1,5-dione B 3.72 335 Ia.68

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid benzylmethylamide B 3.84 357 Ia.69

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid methyl-(2-pyridin-2- ylethyl)amide B 2.47 372 Ia.70

5-(octahydroquinolin-1-yl)- 1-perhydroazocin-1- ylpentane-1,5-dione B 3.84 349 Ia.71

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid cyclooctylamide B 4.10 363 Ia.72

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid dimethylamide B 3.01 281 Ia.73

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid tricyclo[3.3.1.1^(3,7)]decan-1- ylamide B 4.35 387 Ia.74

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid tricyclo[3.3.1.1^(3,7)]decan-2- ylamide B 4.28 387 Ia.75

1-(4-benzoylpiperazin-1- yl)-5-(octahydroquinolin-1- yl)pentane-1,5-dione B 3.34 426 Ia.76

1-(octahydroquinolin-1-yl)- 5-piperidin-1-ylpentane- 1,5-dione A 6.52 321 Ia.77

1-(4-methylpiperazin-1-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione A 4.20 336 Ia.78

1-(4-methylpiperidin-1-yl)- 5-(octahydroquinolin-1- yl)pentane-1,5-dione A 7.02 335 Ia.79

1-(octahydroquinolin-1-yl)- 6-(4-oxopiperidin-1- yl)hexane-1,6-dione B 3.04 349 Ia.80

1-(octahydroquinolin-1-yl)- 6-piperidin-1-ylhexane- 1,6-dione B 3.65 335 Ia.81

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid (3- phenylpropyl)amide B 3.94 385 Ia.82

1-(4-benzylpiperazin-1-yl)- 6-(octahydroquinolin-1- yl)hexane-1,6-dione B 2.74 426 Ia.83

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid phenethylamide B 3.76 371 Ia.84

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid benzylamide B 3.64 357 Ia.85

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid ethylmethylamide B 3.36 309 Ia.86

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid methylpropylamide B 3.62 323 Ia.87

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid butylmethylamide B 3.89 337 Ia.88

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid methylnaphthalen-1- ylmethylamide B 4.24 4.31 421 421 Ia.89

1,6-bis-(octahydroquinolin- 1-yl)hexane-1,6-dione B 4.39 389 Ia.90

6-(octahydroquinolin-1-yl)- 1-perhydroazepin-1- ylhexane-1,6-dione B 3.83 349 Ia.91

1-(3,5-dimethylpiperidin-1- yl)-6-(octahydroquinolin-1- yl)hexane-1,6-dione B 4.11 4.20 363 363 Ia.92

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid benzylmethylamide B 3.93 371 Ia.93

1-(octahydroquinolin-1-yl)- 6-(4-o-tolylpiperazin-1- yl)hexane-1,6-dione B 4.37 426 Ia.94

6-(octahydroquinolin-1-yl)- 1-perhydroazocin-1- ylhexane-1,6-dione B 4.04 363 Ia.95

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid tricyclo[3.3.1.1^(3,7)]decan-1- ylamide B 4.42 401 Ia.96

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid tricyclo[3.3.1.1^(3,7)]decan-2- ylamide B 4.34 401 Ia.97

1-(4-methylpiperidin-1-yl)- 6-(octahydroquinolin-1- yl)hexane-1,6-dione B 3.92 349 Ia.98

1-(3-methylpiperidin-1-yl)- 6-(octahydroquinolin-1- yl)hexane-1,6-dione B 3.92 349 Ia.99

6-(octahydroquinolin-1-yl)- 6-oxohexanoic acid cyclohexylmethylamide B 4.13 363 Ia.100

1-(octahydroisoquinolin-2- yl)-6-(octahydroquinolin-1- yl)hexane-1,6-dione B 4.38 4.47 389 389 Ib.1

Octahydroquinoline-1- carboxylic acid (4-oxo-4- piperidin-1-ylbutyl)amide B 3.42 336 Ib.2

Octahydroquinoline-1- carboxylic acid [3-(3- phenylpropylcarbamoyl) propyl]amide B 3.81 386 Ib.3

Octahydroquinoline-1- carboxylic acid [4-(4- benzylpiperazin-1-yl)-4- oxobutyl]amide B 2.61 427 Ib.4

Octahydroquinoline-1- carboxylic acid (3- phenethylcarbamoylpropyl) amide B 3.61 372 Ib.5

Octahydroquinoline-1- carboxylic acid (3- benzylcarbamoylpropyl) amide B 3.50 358 Ib.6

Octahydroquinoline-1- carboxylic acid [3- (methylpropylcarbamoyl) propyl]amide B 3.39 324 Ib.7

Octahydroquinoline-1- carboxylic acid [3- (butylmethylcarbamoyl) propyl]amide B 3.65 338 Ib.8

Octahydroquinoline-1- carboxylic acid [3- (methylnaphthalen-1- ylmethylcarbamoyl) propyl]amide B 4.08 422 Ib.9

Octahydroquinoline-1- carboxylic acid (4-oxo-4- perhydroazepin-1- ylbutyl)amide B 3.59 350 Ib.10

Octahydroquinoline-1- carboxylic acid [4-(3,5- dimethylpiperidin-1-yl)-4- oxobutyl]amide B 3.87 3.96 364 364 Ib.11

Octahydroquinoline-1- carboxylic acid [3- (benzylmethylcarbamoyl) propyl]amide B 3.71 372 Ib.12

Octahydroquinoline-1- carboxylic acid [4-oxo-4- (4-o-tolylpiperazin-1- yl)butyl]amide B 4.14 427 Ib.13

Octahydroquinoline-1- carboxylic acid (4-oxo-4- perhydroazocin-1- ylbutyl)amide B 3.80 364 Ib.14

Octahydroquinoline-1- carboxylic acid [3- (tricyclo[3.3.1.1^(3,7)]decan-1- ylcarbamoyl)propyl]amide B 4.31 402 Ib.15

Octahydroquinoline-1- carboxylic acid [3- (tricyclo[3.3.1.1^(3,7)]decan-2- ylcarbamoyl)propyl]amide B 4.23 402 Ib.16

Octahydroquinoline-1- carboxylic acid [4-(4- methylpiperidin-1-yl)-4- oxobutyl]amide B 3.69 350 Ib.17

Octahydroquinoline-1- carboxylic acid [4-(3- methylpiperidin-1-yl)-4- oxobutyl]amide B 3.68 350 Ib.18

Octahydroquinoline-1- carboxylic acid [4- (octahydroisoquinolin-2- yl)-4-oxobutyl]amide B 4.14 4.24 390 390 Ib.19

Octahydroquinoline-1- carboxylic acid [3- (cyclohexylmethylcarba- moyl)propyl]amide B 3.89 364 Ib.20

Octahydroquinoline-1- carboxylic acid [3-oxo-3- (4-oxopiperidin-1- yl)propyl]amide B 2.78 336 Ib.21

Octahydroquinoline-1- carboxylic acid (3-oxo-3- piperidin-1-yl propyl)amide B 3.35 322 Ib.22

Octahydroquinoline-1- carboxylic acid [2-(3- phenylpropylcarbamoyl) ethyl]amide B 3.72 372 Ib.23

Octahydroquinoline-1- carboxylic acid [3-(4- benzylpiperazin-1-yl)-3- oxopropyl]amide B 2.56 413 Ib.24

Octahydroquinoline-1- carboxylic acid (2- phenethylcarbamoylethyl) amide B 3.56 358 Ib.25

Octahydroquinoline-1- carboxylic acid (2- benzylcarbamoylethyl) amide B 3.42 344 Ib.26

Octahydroquinoline-1- carboxylic acid [2- (ethylmethylcarbamoyl) ethyl]amide B 3.07 296 Ib.27

Octahydroquinoline-1- carboxylic acid [2- (methylpropylcarbamoyl) ethyl]amide B 3.33 310 Ib.28

Octahydroquinoline-1- carboxylic acid [2- (butylmethylcarbamoyl) ethyl]amide B 3.60 324 Ib.29

Octahydroquinoline-1- carboxylic acid [2- (methylnaphthalen-1- ylmethylcarbamoyl) ethyl]amide B 4.08 408 Ib.30

Octahydroquinoline-1- carboxylic acid (3-oxo-3- perhydroazepin-1- ylpropyl)amide B 3.52 336 Ib.31

Octahydroquinoline-1- carboxylic acid [3-(3,5- dimethylpiperidin-1-yl)-3- oxopropyl]amide B 3.82 3.90 350 350 Ib.32

Octahydroquinoline-1- carboxylic acid [2- (benzylmethylcarbamoyl) ethyl]amide B 3.67 358 Ib.33

Octahydroquinoline-1- carboxylic acid {3-[4-(2- fluorophenyl)piperazin-1- yl]-3-oxopropyl}amide B 3.81 417 Ib.34

Octahydroquinoline-1- carboxylic acid [3-oxo-3- (4-o-tolylpiperazin-1- yl)propyl]amide B 4.09 413 Ib.35

Octahydroquinoline-1- carboxylic acid (3-oxo-3- perhydroazocin-1- ylpropyl)amide B 3.74 350 Ib.36

Octahydroquinoline-1- carboxylic acid [2- (tricyclo[3.3.1.1^(3,7)]decan-2- ylcarbamoyl)ethyl]amide B 4.11 388 Ib.37

Octahydroquinoline-1- carboxylic acid [3-(4- methylpiperidin-1-yl)-3- oxopropyl]amide B 3.62 336 Ib.38

Octahydroquinoline-1- carboxylic acid [3- (octahydroisoquinolin-2- yl)-3-oxopropyl]amide B 4.08 4.17 376 376 Ib.39

Octahydroquinoline-1- carboxylic acid [2- (cyclohexylmethylcarbamoyl) ethyl]amide B 3.83 350 Ib.40

Octahydroquinoline-1- carboxylic acid [3-oxo-3- (4-oxooctahydroquinolin- 1-yl)propyl]amide B 3.44 390 Ib.41

Octahydroquinoline-1- carboxylic acid [3-(3- methylpiperidin-1-yl)-3- oxopropyl]amide B 3.61 336 Ib.42

Octahydroquinoline-1- carbothioic acid S-[3-(3- methylpiperidin-1-yl)-3- oxopropyl] ester B 4.55 353 Ib.43

Octahydroquinoline-1- carbothioic acid S-[3-(4- methylpiperidin-1-yl)-3- oxopropyl] ester B 3.57 353 Ib.44

Octahydroquinoline-1- carbothioic acid S-[2- (tricyclo[3.3.1.1^(3,7)]decan-2- ylcarbamoyl)ethyl] ester B 4.79 405 Ib.45

Octahydroquinoline-1- carbothioic acid S-[2- (tricyclo[3.3.1.1^(3,7)]decan-1- ylcarbamoyl)ethyl] ester B 4.88 405 Ib.46

Octahydroquinoline-1- carbothioic acid S-[3-(3,5- dimethylpiperidin-1-yl)-3- oxopropyl] ester B 4.75 367 Ib.47

Octahydroquinoline-1- carbothioic acid S-(3-oxo- 3-perhydroazepin-1- ylpropyl) ester B 4.56 353 Ib.48

Octahydroquinoline-1- carbothioic acid S-[2- (methylpropylcarbamoyl) ethyl] ester B 4.14 327 Ib.49

Octahydroquinoline-1- carbothioic acid S-[2- (ethylmethylcarbamoyl) ethyl] ester B 3.88 313 Ib.50

Octahydroquinoline-1- carbothioic acid S-(3-oxo- 3-piperidin-1-ylpropyl) ester B 4.20 339 Ib.51

Octahydroquinoline-1- carbothioic acid S-[3-oxo- 3-(4-oxopiperidin-1- yl)propyl] ester B 3.49 353 Ib.52

Octahydroquinoline-1- carbothioic acid S-[2- (cyclohexylmethyl- carbamoyl)ethyl] ester B 4.67 364 Ib.53

Octahydroquinoline-1- carbothioic acid S-[3-oxo- 3-(4-o-tolylpiperazin-1- yl)propyl] ester B 4.86 430 Ib.54

Octahydroquinoline-1- carbothioic acid S-[2- (benzylmethylcarbamoyl) ethyl] ester B 4.42 375 Ib.55

Octahydroquinoline-1- carbothioic acid S-[2- (methylnaphthalen-1- ylmethylcarbamoyl) ethyl]ester B 4.78 425 Ib.56

Octahydroquinoline-1- carbothioic acid S-[2- (butylmethylcarbamoyl) ethyl]ester B 4.41 341 Ib.57

Octahydroquinoline-1- carbothioic acid S-(2- benzylcarbamoylethyl) ester B 4.06 361 Ib.58

Octahydroquinoline-1- carbothioic acid S-[3-(4- benzylpiperazin-1-yl)-3- ozopropyl] ester B 2.98 430 Ib.59

Octahydroquinoline-1- carbothioic acid S-(3-oxo- 3-perhydroazocin-1- ylpropyl) ester B 4.58 367 Ib.60

Octahydroquinoline-1- carbothioic acid S-{3-[4- (2-fluorophenyl)piperazin- 1-yl]-3-oxopropyl} ester B 4.59 434 Ib.61

Octahydroquinoline-1- carbothioic acid S-(2- phenethylcarbamoylethyl) ester B 4.20 375 Ib.62

Octahydroquinoline-1- carbothioic acid S-[2-(3- phenylpropylcarbamoyl) ethyl] ester B 4.34 389 Im.1

1-[4-(octahydroquinoline-1- sulfonyl)butyryl]piperidin- 4-one B 3.16 371 Im.2

4-(octahydroquinoline-1- sulfonyl)-1-piperidin-1- ylbutan-1-one B 3.79 357 Im.3

1-(4-hydroxypiperidin-1- yl)-4-(octahydroquinoline- 1-sulfonyl)butan-1-one B 2.96 373 Im.4

4-(octahydroquinoline-1- sulfonyl)-1- perhydroazepin-1-ylbutan- 1-one B 3.96 371 Im.5

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-4- (octahydroquinoline-1- sulfonyl)butan-1-one B 3.92 464 Im.6

1-(3.5-dimethylpiperidin-1- yl)-4-(octahydroquinoline- 1-sulfonyl)butan-1-one B 4.34 385 Im.7

4-(octahydroquinoline-1- sulfonyl)-1-(4-o- tolylpiperazin-1-yl)butan- 1-one B 4.49 448 Im.8

4-(octahydroquinoline-1- sulfonyl)-1- perhydroazocin-1-ylbutan- 1-one B 4.17 385 Im.9

1-((R)-3-hydroxypiperidin- 1-yl)-4- (octahydroquinoline-1- sulfonyl)butan-1-one B 3.07 373 Im.10

1-(4-benzhydrylpiperazin- 1-yl)-4- (octahydroquinoline-1- sulfonyl)butan-1-one B 3.82 524 Im.11

1-(4-methylpiperidin-1-yl)- 4-(octahydroquinoline-1- sulfonyl)butan-1-one B 4.06 371 Im.12

1-(3-methylpiperidin-1-yl)- 4-(octahydroquinoline-1- sulfonyl)butan-1-one B 4.05 371 Im.13

1-(octahydroisoquinolin-2- yl)-4-(octahydroquinoline- 1-sulfonyl)butan-1-one B 4.50 4.59 411 411 Im.14

N-cyclohexyl-N-methyl-4- (octahydroquinoline-1- sulfonyl)butyramide B 4.26 385 Im.15

1-(3,3-difluoropiperidin-1- yl)-4-(octahydroquinoline- 1-sulfonyl)butan-1-one B 3.80 393 Im.16

1-(4,4-difluoropiperidin-1- yl)-4-(octahydroquinoline- 1-sulfonyl)butan-1-one B 3.81 393 Ia.101

1-(octahydroisoquinolin-2- yl)-2-piperidin-1-ylethane- 1,2-dione A 6.28 6.45 279 279 Ia.102

1-(4-methylpiperazin-1-yl)- 2-(octahydroisoquinolin-2- yl)ethane-1,2-dione A 4.04 294 Ia.103

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-2- (octahydroisoquinolin-2- yl)ethane-1,2-dione A 7.03 7.17 386 386 Ia.104

1-(3,5-dimethylpiperidin- 1-yl)-2- (octahydroisoquinolin-2- yl)ethane-1,2-dione A 7.41 7.53 307 307 Ia.105

1-(4-methylpiperidin-1-yl)- 2-(octahydroisoquinolin-2- yl)ethane-1,2-dione A 6.86 7.01 293 293 Ia.106

1-(3-methylpiperidin-1-yl)- 2-(octahydroisoquinolin-2- yl)ethane-1,2-dione A 6.83 6.99 293 293 Ia.107

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 2-(octahydroisoquinolin-2- yl)ethane-1,2-dione A 6.20 6.38 309 309 Ia.108

1-(octahydroisoquinolin-2- yl)-2-(4-o-tolylpiperazin-1- yl)ethane-1,2-dione A 7.98 370 Ia.109

1-(4-benzylpiperidin-1-yl)- 2-(octahydroisoquinolin-2- yl)ethane-1,2-dione A 8.04 369 Ia.110

1-(4-benzhydrylpiperazin- 1-yl)-2- (octahydroisoquinolin-2- yl)ethane-1,2-dione A 7.63 7.80 446 446 Ia.111

1,2-bis- (octahydroisoquinolin-2- yl)ethane-1,2-dione A 8.06 333 Ia.112

1-(octahydroisoquinolin-2- yl)-3-piperidin-1- ylpropane-1,3-dione A 6.11 6.28 293 293 Ia.113

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-3- (octahydroisoquinolin-2- yl)propane-1,3-dione A 6.47 6.64 400 400 Ia.114

1-(3,5-dimethylpiperidin-1- yl)-3- (octahydroisoquinolin-2- yl)propane-1,3-dione A 7.20 7.33 321 321 Ia.115

1-(4-methylpiperidin-1-yl)- 3-(octahydroisoquinolin-2- yl)propane-1,3-dione A 6.66 6.81 307 307 Ia.116

1-(3-methylpiperidin-1-yl)- 3-(octahydroisoquinolin-2- yl)propane-1,3-dione A 6.63 6.79 307 307 Ia.117

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 3-(octahydroisoquinolin-2- yl)propane-1,3-dione A 5.91 6.09 323 323 Ia.118

1-(octahydroisoquinolin-2- yl)-3-(4-o-tolylpiperazin-1- yl)propane-1,3-dione A 7.57 7.70 384 384 Ia.119

1-(4-benzylpiperidin-1-yl)- 3-(octahydroisoquinolin-2- yl)propane-1,3-dione A 7.73 7.85 383 383 Ia.120

1-(4-benzhydrylpiperazin- 1-yl)-3- (octahydroisoquinolin-2- yl)propane-1,3-dione A 6.34 6.48 460 460 Ia.121

1-(4-methylpiperazin-1-yl)- 3-(octahydroisoquinolin-2- yl)propane-1,3-dione A 4.06 308 Ia.122

1-(6,7-dimethoxy-3,4- dihydro-1-H-isoquinolin-2- yl)-2- (octahydroisoquinolin-2- yl)ethane-1,2-dione A 6.65 387 Ia.123

1-(octahydroisoquinolin-2- yl)-4-piperidin-1-ylbutane- 1,4-dione A 6.37 6.56 307 307 Ia.124

1-(4-methylpiperazin-1-yl)- 4-(octahydroisoquinolin-2- yl)butane-1,4-dione A 4.32 322 Ia.125

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-4- (octahydroisoquinolin-2- yl)butane-1,4-dione A 6.52 6.71 414 414 Ia.126

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 4-(octahydroisoquinolin-2- yl)butane-1,4-dione A 6.15 6.34 337 337 Ia.127

1-(octahydroisoquinolin-2- yl)-4-(4-o-tolylpiperazin-1- yl)butane-1,4-dione A 7.66 7.81 398 398 Ia.128

1-(4-benzylpiperidin-1-yl)- 4-(octahydroisoquinolin-2- yl)butane-1,4-dione A 7.90 8.03 397 397 Ia.129

1,4-bis- (octahydroisoquinolin-2- yl)butane-1,4-dione A 7.94 8.09 361 361 Ia.130

1-(3,5-dimethylpiperidin-1- yl)-4- (octahydroisoquinolin-2- yl)butane-1,4-dione A 7.44 7.59 335 335 Ia.131

1-(4-methylpiperidin-1-yl)- 4-(octahydroisoquinolin-2- yl)butane-1,4-dione A 6.91 7.08 321 321 Ia.132

1-(3-methylpiperidin-1-yl)- 4-(octahydroisoquinolin-2- yl)butane-1,4-dione A 6.89 7.06 321 321 Ia.133

1-(4-benzhydrylpiperazin- 1-yl)-4- (octahydroisoquinolin-2- yl)butane-1,4-dione A 6.24 6.34 474 474 Ia.134

1-(octahydroisoquinolin-2- yl)-5-piperidin-1- ylpentane-1,5-dione A 6.51 6.70 321 321 Ia.135

1-(4-methylpiperazin-1-yl)- 5-(octahydroisoquinolin-2- yl)pentane-1,5-dione A 4.27 336 Ia.136

1-[4-(2- methoxyphenyl)piperazin- 1-yl]-5- (octahydroisoquinolin-2- yl)pentane-1,5-dione A 6.74 6.93 428 428 Ia.137

1-(3,5-dimethylpiperidin-1- yl)-5- (octahydroisoquinolin-2- yl)pentane-1,5-dione A 7.52 7.68 349 349 Ia.138

1-(3-methylpiperidin-1-yl)- 5-(octahydroisoquinolin-2- yl)pentane-1,5-dione A 7.01 7.19 335 335 Ia.139

1-((2S,6R)-2,6- dimethylmorpholin-4-yl)- 5-(octahydroisoquinolin-2- yl)pentane-1,5-dione A 6.26 6.45 351 351 Ia.140

1-(octahydroisoquinolin-2- yl)-5-(4-o-tolylpiperazin-1- yl)pentane-1,5-dione A 7.85 8.01 412 412 Ia.141

1-(4-benzylpiperidin-1-yl)- 5-(octahydroisoquinolin-2- yl)pentane-1,5-dione A 8.01 8.16 411 411 Ia.142

1,5-bis- (octahydroisoquinolin-2- yl)pentane-1,5-dione A 8.04 8.21 375 375 Ia.143

1-(4-methylpiperidin-1-yl)- 5-(octahydroisoquinolin-2- yl)pentane-1,5-dione A 7.03 7.22 335 335 Ia.144

1-(4-benzhydrylpiperazin- 1-yl)-5- (octahydroisoquinolin-2- yl)pentane-1,5-dione A 6.53 6.67 488 448 Ia.145

1-(3,4-dihydro-2-H- quinolin-1-yl)-5- (octahydroisoquinolin-2- yl)pentane-1,5-dione A 7.49 7.66 369 370 Ia.146

1-(octahydroisoquinolin-2- yl)-5-(1-oxo-3,4-dihydro- 1-H-isoquinolin-2- yl)pentane-1,5-dione A 7.73 7.90 383 383 Ia.147

1-(octahydroisoquinolin-2- yl)-6-(4-oxopiperidin-1- yl)hexane-1,6-dione B 3.04 3.14 349 349 Ia.148

1-(octahydroisoquinolin-2- yl)-6-piperidin-1-ylhexane- 1,6-dione B 3.64 3.75 335 335 Ia.149

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid (3- phenylpropyl)amide B 3.93 4.02 385 385 Ia.150

1-(4-benzylpiperazin-1-yl)- 6-(octahydroisoquinolin-2- yl)hexane-1,6-dione B 2.77 2.83 426 426 Ia.151

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid phenethylamide B 3.75 3.84 371 371 Ia.152

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid benzylamide B 3.63 3.73 357 357 Ia.153

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid ethylmethylamide B 3.36 3.46 309 309 Ia.154

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid methylpropylamide B 3.61 3.72 323 323 Ia.155

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid butylmethylamide B 3.88 3.98 337 337 Ia.156

6-(octahydroisoquinolin-2- yl)-1-perhydroazepin-1- ylhexane-1,6-dione B 3.82 3.92 349 349 Ia.157

1-(3,5-dimethylpiperidin-1- yl)-6- (octahydroisoquinolin-2- yl)hexane-1,6-dione B 4.20 4.29 363 363 Ia.158

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid benzylmethylamide B 3.92 4.02 371 371 Ia.159

1-[4-(2- fluorophenyl)piperazin-1- yl]-6- (octahydroisoquinolin-2- yl)hexane-1,6-dione B 4.08 4.17 430 430 Ia.160

1-(octahydroisoquinolin-2- yl)-6-(4-o-tolylpiperazin-1- yl)hexane-1,6-dione B 4.35 4.44 426 426 Ia.161

6-(octahydroisoquinolin-2- yl)-1-perhydroazocin-1- ylhexane-1,6-dione B 4.03 4.13 363 363 Ia.162

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid tricyclo[3.3.1.1^(3,7)]ldecan-1- ylamide B 4.41 4.50 401 401 Ia.163

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid tricyclo[3.3.1.1^(3,7)]decan- 2-ylamide B 4.32 4.41 401 401 Ia.164

1-(4-methylpiperidin-1-yl)- 6-(octahydroisoquinolin-2- yl)hexane-1,6-dione B 3.92 4.02 349 349 Ia.165

1-(3-methylpiperidin-1-yl)- 6-(octahydroisoquinolin-2- yl)hexane-1,6-dione B 3.91 4.02 349 349 Ia.166

1,6-bis- (octahydroisoquinolin-2- yl)hexane-1,6-dione B 4.47 4.56 389 389 Ia.167

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid cyclohexylmethylamide B 4.12 4.21 363 363 Ib.63

Octahydroisoquinoline-2- carboxylic acid [2-(3- phenylpropylcarbamoyl) ethyl]amide B 3.72 3.80 372 372 Ib.64

Octahydroisoquinoline-2- carboxylic acid (2- benzylcarbamoylethyl) amide B 3.42 3.50 344 344 Ib.65

Octahydroisoquinoline-2- carboxylic acid [2- (ethylmethylcarbamoyl) ethyl]amide B 3.06 3.17 296 296 Ib.66

Octahydroisoquinoline-2- carboxylic acid [2- (methylpropylcarbamoyl) ethyl]amide B 3.32 3.42 310 310 Ib.67

Octahydroisoquinoline-2- carboxylic acid [3-(3,5- dimethylpiperidin-1-yl)-3- oxopropyl]amide B 3.91 3.98 350 350 Ib.68

Octahydroisoquinoline-2- carboxylic acid [2- (benzylmethylcarbamoyl) ethyl]amide B 3.66 3.75 358 358 Ib.69

Octahydroisoquinoline-2- carboxylic acid [3-(4- methylpiperidin-1-yl)-3- oxopropyl]amide B 3.62 3.71 336 336 Ib.70

Octahydroisoquinoline-2- carboxylic acid [3-(3- methylpiperidin-1-yl)-3- oxopropyl]amide B 3.61 3.70 336 336 Ib.71

Octahydroisoquinoline-2- carboxylic acid [2- (cyclohexylmethylcarba- moyl)ethyl]amide B 3.83 3.91 350 350 Ib.72

Octahydroisoquinoline-2- carboxylic acid (4-oxo-4- piperidin-1-ylbutyl)amide B 3.41 3.51 336 336 Ib.73

Octahydroisoquinoline-2- carboxylic acid [3-(3- phenylpropylcarbamoyl) propyl]amide B 3.88 386 Ib.74

Octahydroisoquinoline-2- carboxylic acid [4-(4- benzylpiperazin-1-yl)-4- oxobutyl]amide B 2.67 427 Ib.75

Octahydroisoquinoline-2- carboxylic acid (3- phenethylcarbamoylpropyl) amide B 3.70 372 Ib.76

Octahydroisoquinoline-2- carboxylic acid (3- benzylcarbamoylpropyl) amide B 3.58 358 Ib.77

Octahydroisoquinoline-2- carboxylic acid [3- (ethylmethylcarbamoyl) propyl]amide B 3.24 310 Ib.78

Octahydroisoquinoline-2- carboxylic acid [3- (methylpropylcarbamoyl) propyl]amide B 3.37 3.47 324 324 Ib.79

Octahydroisoquinoline-2- carboxylic acid [3- (butylmethylcarbamoyl) propyl]amide B 3.74 338 Ib.80

Octahydroisoquinoline-2- carboxylic acid [3- (methylnaphthalen-1- ylmethylcarbamoyl) propyl]amide B 4.15 422 Ib.81

Octahydroisoquinoline-2- carboxylic acid (4-oxo-4- perhydroazepin-1- ylbutyl)amide B 3.57 3.67 350 350 Ib.82

Octahydroisoquinoline-2- carboxylic acid [4-(3,5- dimethylpiperidin-1-yl)-4- oxobutyl]amide B 3.95 4.04 364 364 Ib.83

Octahydroisoquinoline-2- carboxylic acid [3- (benzylmethylcarbamoyl) propyl]amide B 3.69 3.78 372 372 Ib.84

Octahydroisoquinoline-2- carboxylic acid {4-[4-(2- fluorophenyl)piperazin-1- yl]-4-oxobutyl}amide B 3.85 3.94 431 431 Ib.85

Octahydroisoquinoline-2- carboxylic acid [4-oxo-4- (4-o-tolylpiperazin-1- yl)butyl]amide B 4.12 4.20 427 427 Ib.86

Octahydroisoquinoline-2- carboxylic acid (4-oxo-4- perhydroazocin-1- ylbutyl)amide B 3.78 3.87 364 364 Ib.87

Octahydroisoquinoline-2- carboxylic acid [3- (tricyclo[3.3.1.1^(3,7)]decan-1- ylcarbamoyl)propyl]amide B 4.38 402 Ib.88

Octahydroisoquinoline-2- carboxylic acid [4-(4- methylpiperidin-1-yl)-4- oxobutyl]amide B 3.67 3.77 350 350 Ib.89

Octahydroisoquinoline-2- carboxylic acid [4-(3- methylpiperidin-1-yl)-4- oxobutyl]amide B 3.66 3.76 350 350 Ib.90

Octahydroisoquinoline-2- carboxylic acid [3- (cyclohexylmethylcarba- moyl)propyl]amide B 3.87 3.96 364 364 Ib.91

Octahydroisoquinoline-2- carbothioic acid S-[3- (cyclohexylmethylcarba- moyl)propyl] ester B 4.49 381 Ib.92

Octahydroisoquinoline-2- carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide B 4.10 4.17 376 376 Ib.93

Octahydroisoquinoline-2- carboxylic acid [3-oxo-3- (4-oxooctahydroquinolin- 1-yl)propyl]amide B 3.46 3.53 390 390 Ib.94

Octahydroquinoline-1- carboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide B 4.15 390 Ib.95

Octahydroisoquinoline-2- carboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide B 4.22 390 Ib.96

Octahydroisoquinoline-2- carboxylic acid [3- (octahydroisoquinolin-2- yl)-3-oxopropyl]amide B 4.17 4.25 376 376 Ib.97

Octahydroquinoline-1- carboxylic acid N-[3- [(3s,5s,7s)-adamantan-1- ylamino-3-oxopropyl] amide B 4.18 388 Im.17

1-[4- (octahydroisoquinoline-2- sulfonyl)butyryl]piperidin- 4-one B 3.25 3.31 371 371 Im.18

4-(octahydroisoquinoline- 2-sulfonyl)-1-piperidin-1- ylbutan-1-one B 3.93 357 Im.19

1-(4-hydroxypiperidin-1- yl)-4- (octahydroisoquinoline-2- sulfonyl)butan-1-one B 3.04 3.11 373 373 Im.20

4-(octahydroisoquinoline- 2-sulfonyl)-1- perhydroazepin-1- ylbutan-1-one B 4.02 4.09 371 371 Im.21

1-(3,5-dimethylpiperidin-1- yl)-4- (octahydroisoquinoline-2- sulfonyl)butan-1-one B 4.37 4.45 385 385 Im.22

4-(octahydroisoquinoline- 2-sulfonyl)-1- perhydroazocin-1-ylbutan- 1-one B 4.23 4.30 385 385 Im.23

1-((R)-3-hydroxypiperidin- 1-yl)-4- (octahydroisoquinolin-2- sulfonyl)butan-1-one B 3.15 3.22 373 373 Im.24

1-(4-methylpiperidin-1-yl)- 4-(octahydroisoquinoline- 2-sulfonyl)butan-1-one B 4.12 4.19 371 371 Im.25

1-(3-methylpiperidin-1-yl)- 4-(octahydroisoquinoline- 2-sulfonyl)butan-1-one B 4.11 4.18 371 371 Im.26

N-cyclohexyl-N-methyl-4- (octahydroisoquinoline-2- sulfonyl)butyramide B 4.31 4.37 385 385 Im.27

1-(3,3-difluoropiperidin-1- yl)-4- (octahydroisoquinoline-2- sulfonyl)butan-1-one B 3.87 3.93 393 393 Im.28

1-(4,4-difluoropiperidin-1- yl)-4- (octahydroisoquinoline-2- sulfonyl)butan-1-one B 3.87 3.94 393 393 Im.29

4-(octahydroquinoline-1- sulfonyl)-1- (octahydroquinolin-1- yl)butan-1-one B 4.51 411 Im.30

4-(octahydroisoquinoline- 2-sulfonyl)-1- (octahydroisoquinolin-2- yl)butan-1-one B 4.63 4.70 411 411 Ia.168

1-(octahydroisoquinolin-2- yl)-4-(6- oxooctahydroindol-1- yl)butane-1,4-dione B 4.33 4.41 361 361 Ia.169

1-(octahydroisoquinolin-2- yl)-5-(6- oxooctahydroindol-1- yl)pentane-1,5-dione B 4.38 4.48 375 375 Ia.170

1-[4-(2- fluorophenyl)piperazin-1- yl]-6-(octahydroquinolin-1- yl)hexane-1,6-dione B 4.09 430 Ia.171

1-(octahydroquinolin-1-yl)- 6-(4- oxooctahydroquinolin-1- yl)hexane-1,6-dione B 3.72 403 Ia.172

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[3- (1H-imidazol-1- yl)propyl]amide B 2.29 361 Ia.173

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (2,4- dichlorophenethyl)amide B 4.20  425, 427 Ia.174

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (5-methoxy-1H-indol-3- yl)ethyl]amide B 3.47 426 Ia.175

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (3,4- dimethoxyphenethyl]amide B 3.41 417 Ia.176

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (pyridin-2-yl)ethyl]amide B 2.34 358 Ia.177

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- aminophenethyl)amide B 2.44 372 Ia.178

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (3,3-diphenylpropyl)amide B 4.28 447 Ia.179

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- methoxyphenethyl)amide B 3.74 387 Ia.180

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- chlorophenethyl)amide B 3.88 391 Ia.181

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- sulfamoylphenethyl)amide B 2.97 436 Ia.182

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- phenoxyethyl)amide B 3.67 373 Ia.183

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(3- methoxyphenethyl)amide B 3.65 387 Ia.184

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(3- chlorophenethyl)amide B 3.92 391 Ia.185

5-(octahydroquinolin-1)- yl)-5-oxopentanoic acid N- [2-(benzo[d][1,3]dioxol-5- yl)ethyl]amide B 3.56 401 Ia.186

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[(1- phenylcyclopropyl)methyl] amide B 3.92 383 Ia.187

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (naphthalen-2- yl)ethyl]amide B 4.05 407 Ia.188

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(R)-2-phenyl-2- hydroxyethyl]amide B 3.19 373 Ia.189

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(1R,2S)-1-phenyl-1- hydroxypropan-2-yl]amide B 3.37 387 Ia.190

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (2,3-dihydro-1H-inden-2- yl)amide B 3.77 369 Ia.191

(2S)-3-(4-hydroxyphenyl)- 2-[5-(octahydroquinolin-1- yl)-5- oxopentanamide]propanoic acid methyl ester B 3.21 431 Ia.192

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (thiophen-2-yl)ethyl]amide B 3.58 363 Ia.193

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- chlorophenethyl)amide B 3.93 391 Ia.194

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (2,2-diphenylpropyl)amide B 4.39 447 Ia.195

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (2,2-diphenylethyl)amide B 4.16 433 Ia.196

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- methylphenethyl)amide B 3.88 371 Ia.197

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- methoxyphenethyl)amide B 3.61 387 Ia.198

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(3- fluorophenethyl)amide B 3.72 375 Ia.199

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- hydroxyphenethyl)amide B 3.10 373 Ia.200

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(1- hydroxyl-1-(4- hydroxyphenyl)propan-2- yl)amide B 2.88 403 Ia.201

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(1- hydroxyl-1-(3- hydroxyphenyl)propan-2- yl)amide B 3.00 403 Ia.202

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (5-hydroxyl-1H-indol-3- yl)ethyl]amide B 3.04 412 Ia.203

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(R)-1-amino-3-phenyl-1- oxopropan-2-yl]amide B 3.19 400 Ia.204

N-methyl-5- (octahydroquinolin-1-yl)-5- oxopentanoic acid N-((4- phenyltetrahydro-2H- pyran-4-yl)methyl)amide B 3.89 441 Ia.205

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- phenylpropyl)amide B 4.02 385 Ia.206

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[2- (naphthalen-1- yl)ethyl]amide B 4.06 407 Ia.207

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[(4- phenyltetrahydro-2H- pyran-4-yl)methyl]amide B 3.06 427 Ia.208

5-(octahydroquinolin-1-yl)- 5-oxopropanoic acid N- [(S)-3-phenyl-1-oxo-1- (pyrrolidin-1-yl)propan-2- yl]amide B 3.65 454 Ia.209

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(S)-1-(cyclohexylamino)- 3-phenylpropane-1-oxo-2- yl]amide B 4.06 482 Ia.210

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(S)-1-amino-3-phenyl-1- oxopropan-2-yl]amide B 3.19 400 Ia.211

N-(2-amino-2-oxoethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanoic acid N- phenethylamide B 3.41 414 Ia.212

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(S)-1-amino-3-(1H-indol- 3-yl)-1-oxopropan-2- yl]amide B 3.15 439 Ia.213

1-(2-phenyl-4- methylpiperazin-1-yl)-5- (octahydroquinolin-1- yl)pentane-1,5-dione B 2.58 412 Ia.214

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzyl-N-ethylamide B 4.06 371 Ia.215

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- methoxybenzyl)amide B 3.50 373 Ia.216

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- (trifluoromethyl)benzyl) amide B 3.97 411 Ia.217

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(R)-1-phenylethyl]amide B 3.70 357 Ia.218

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N,N- dibenzylamide B 4.53 433 Ia.219

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (9H-fluoren-9-yl)amide B 4.18 417 Ia.220

2-(N-benzyl-5- (octahydroquinolin-1-yl)-5- oxopentanamide)acetic acid ethyl ester B 4.12 429 Ia.221

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [cyano(phenyl)methyl] amide B 3.68 368 Ia.222

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzhydrylamide B 4.15 419 Ia.223

(2R)-2-(5- (octahydroquinolin-1-yl)- 5-oxopentanamido)-2- phenylacetic acid methyl ester B 3.67 401 Ia.224

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (1,2,3,4- tetrahydronaphthalen-1- yl)amide B 3.96 383 Ia.225

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (benzo[d][1,3]dioxol-5-yl methyl)amide B 3.46 387 Ia.226

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzyl-N-butylamide B 4.51 399 Ia.227

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzyl-N-[2- (dimethylamino)ethyl] amide B 2.83 414 Ia.228

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzyl-N-isopropylamide B 4.22 385 Ia.229

2-[N-[3-(1H-imidazol-1- yl)propyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 2.67 447 Ia.230

2-[5-(octahydroquinolin-1- yl)-5-oxo-N-(4- sulfamoylphenethyl)pentan- amido]acetic acid ethyl ester B 3.43 522 Ia.231

2-[N-[2-(5-methoxy-1H- indol-3-yl)ethyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 3.92 512 Ia.232

2-[5-(octahydroquinolin-1- yl)-5-oxo-N-[2-(pyridin-2- yl)ethyl]pentanamido] acetic acid ethyl ester B 2.79 444 Ia.233

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- amino-2-oxoethyl)-N- benzylamide B 3.28 400 Ia.234

3-[N-benzyl-5- (octahydroquinolin-1-yl)-5- oxopentanamido]propanoic acid ethyl ester B 4.15 443 Ia.235

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzyl-N-(2- hydroxyethyl)amide B 3.47 387 Ia.236

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (1,2-diphenylethyl)amide B 4.21 433 Ia.237

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- benzhydryl-N-methylamide B 4.53 433 Ia.238

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(4- chlorobenzyl)amide B 3.82 377 Ia.239

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[4- (trifluoromethoxy)benzyl] amide B 4.06 427 Ia.240

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[3- (trifluoromethoxy)benzyl] amide B 4.06 427 Ia.241

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-[3- (trifluoromethyl)benzyl] amide B 3.97 411 Ia.242

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- phenethyl-N-[2- (phenethylamino)-2- oxoethyl]amide B 4.25 518 Ia.243

5-(octahydroquinolin-1-yl) 5-oxopentanoic acid N-[2- oxo-2-{[2-(thiophen-2- yl)ethyl]amino}ethyl]-N- [2-(thiophen-2- yl)ethyl]amide B 4.11 530 Ia.244

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(S)-3-phenyl-1- hydroxypropan-2-yl]amide B 3.31 387 Ia.245

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- [(S)-1-phenylethyl]amide B 3.70 357 Ia.246

2-[N-(4- hydroxyphenethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 3.59 459 Ia.247

2-(N-(3,4- dimethoxyphenethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 3.91 503 Ia.248

2-[N-[2-(1H-indol-3- yl)ethyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 4.04 482 Ia.249

2-[N-[2-(5-hydroxy-1H- indol-3-yl)ethyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 3.47 498 Ia.250

2-[N-(4-nitrophenethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 4.10 488 Ia.251

2-(N-(2,4- dichlorophenethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 4.73 511 Ia.252

2-[N-(4-chlorophenethyl)- 5-(octahydroquinolin-1-yl)- 5-oxopentanamido]acetic acid ethyl ester B 4.45 477 Ia.253

2-[N-(4- methoxyphenethyl)-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid ethyl ester B 4.14 473 Ia.254

2-[5-(octahydroquinolin-1- yl)-5-oxo-N-[2- (trifluoromethyl)benzyl] pentanamido]acetic acid methyl ester B 4.27 483 Ia.255

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N-(2- amino-2-oxoethyl)-N-[2- (1H-indol-3-yl)ethyl]amide B 3.34 453 Ia.256

5-(octahydroquinolin-1-yl)- 5-oxopentanoic acid N- (2,4-dichlorophenethyl)-N- [2-[(2,4- dichlorophenethyl)amino]- 2-oxoethyl]amide B 5.13  654, 656 Ia.257

2-[N-[4- (benzyloxy)benzyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]acetic acid methyl ester B 4.46 521 Ia.258

2-[5-(octahydroquinolin-1- yl)-5-oxo-N-(3- phenoxybenzyl)pentan- amido]acetic acid ethyl ester B 4.65 521 Ia.259

2-[5-(octahydroquinolin-1- yl)-5-oxo-N-(4- phenylbutyl)pentanamido] acetic acid ethyl ester B 4.54 471 Ia.260

3-[N-[4- (benzyloxy)benzyl]-5- (octahydroquinolin-1-yl)-5- oxopentanamido]propanoic acid methyl ester B 4.48 535 Ia.261

6-(octahydroisoquinolin-2- yl)-6-oxohexanoic acid N- methyl-N-(naphthalen-1- ylmethyl)amide B 4.31 4.40 421 421 Ia.262

1-(octahydroisoquinolin-2- yl)-6-(4- oxooctahydroquinolin-1- yl)hexane-1,6-dione B 3.72 3.81 403 403 Ia.263

5-(octahydro-quinolin-1- yl)-5-oxo-pentanoic acid (3-methyl-10,11-dihydro- 5H- dibenzo[a,d]cyclohepten-5- yl)amide C 5.01 459 Ia.264

5-(octahydro-quinolin-1- yl)-5-oxo-pentanoic acid (3-ethyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5- yl)amide C 5.20 473 Ia.265

5-[(R)-1-phenyl-3,4- dihydro-1H-isoquinolin-2- yl]-1-(octahydro-quinolin- 1-yl)-pentane-1,5-dione C 5.02 445 Ia.266

5-(octahydro-quinolin-1- yl)-5-oxo-pentanoic acid (1-phenyl- cyclobutylmethyl)amide C 4.64 397 Ia.267

5-(octahydro-quinolin-1- yl)-5-oxo-pentanoic acid (2-cyclohexyl-2-phenyl- ethyl)amide C 5.19 439

Ex. Ie.1 1-[5-(octahydroquinolin-1-yl)-5-oxopentyl]-3-tricyclo[3.3.1.1^(3,7)]decan-1-ylurea

35 mg (0.15 mmol) of intermediate Vc.4 are dissolved in 2 mL of anhydrous THF and 23 μL (0.25 mmol) of Et₃N. Once dissolved 17.3 mg (0.1 mmol) of 1-adamantyl isocyanate are slowly added and it is refluxed for 2 days. AcOEt is then added and the resulting solution is sequentially washed with water, 1N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure yielding 47.5 mg of a yellowish oil identified as example Ie.1. Method B: tr: 4.27 min; m/z: 416.

The following examples were prepared in a manner similar to example Ie.1.

Ex. structure name method tr (min) m/z Ie.2

1-[3-(octahydroquinolin- 1-yl)-3-oxopropyl]-3- phenylurea B 3.49 330 Ie.3

1-s-butyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea B 3.28 3.56 310 310 Ie.4

1-[3-(octahydroquinolin- 1-yl)-3-oxopropyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylurea B 4.18 388 Ie.5

1-[3-(octahydroquinolin- 1-yl)-3-oxopropyl]-3-(4- thiophen-2- yltetrahydropyran-4- yl)urea B 3.40 420 Ie.6

1-cyclohexyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.55 336 Ie.7

1-benzyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.28 344 Ie.8

1-(4-fluorophenyl)-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.56 348 Ie.9

1-t-butyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.25 310 Ie.10

1-isopropyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 5.65 296 Ie.11

1-furan-2-ylmethyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 5.85 334 Ie.12

1-(6-fluoro-4-H-1,3- benzodioxin-8-yl)-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.75 406 Ie.13

1-cycloheptyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]urea A 6.93 350 Ie.18

1-benzyl-3-[4- (octahydroquinolin-1-yl)- 4-oxobutyl]urea B 3.44 358 Ie.19

1-[4-(octahydroquinolin- 1-yl)-4-oxobutyl]-3- thiophen-2-ylurea B 3.41 350 Ie.20

1-[4-(octahydroquinolin- 1-yl)-4-ozobutyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylurea B 4.18 402 Ie.21

1-cyclohexyl-3-[4- (octahydroquinolin-1-yl)- 4-oxobutyl]urea B 3.59 350 Ie.22

1-cycloheptyl-3-[4- (octahydroquinolin-1-yl)- 4-oxobutyl]urea B 3.80 364 Ie.23

1-cyclohexyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.69 364 Ie.24

1-[5-(octahydroquinolin- 1-yl)-5-oxopentyl]-3- phenylurea B 3.61 358 Ie.25

1-benzyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.55 372 Ie.26

1-(4-fluorophenyl)-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.67 376 Ie.27

1-s-butyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.44 338 Ie.28

1-t-butyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.55 338 Ie.29

1-isopropyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.24 324 Ie.30

1-furan-2-ylmethyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.33 362 Ie.31

1-cycloheptyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]urea B 3.88 378 Ig.1

Octahydroquinoline-1- carboxylic acid [3-(3- cyclohexylureido)propyl] amide B 3.60 365 Ig.2

Octahydroquinoline-1- carboxylic acid [3-(3- phenylureido)propyl]amide B 3.52 359 Ig.3

Octahydroquinoline-1- carboxylic acid [3-(3- benzylureido)propyl]amide B 3.45 373 Ig.4

Octahydroquinoline-1- carboxylic acid {3-[3-(4- fluorophenyl)ureido] propyl}amide B 3.58 377 Ig.5

Octahydroquinoline-1- carboxylic acid [3-(3-s- butylureido)propyl]amide B 3.33 339 Ig.6

Octahydroquinoline-1- carboxylic acid [3-(3-t- butylureido)propyl]amide B 3.48 339 Ig.7

Octahydroquinoline-1- carboxylic acid [3-(3- furan-2-ylmethylureido) propyl]amide B 3.22 363 Ig.8

Octahydroquinoline-1- carboxylic acid [3-(3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylureido)propyl]amide B 4.26 417 Ig.9

Octahydroquinoline-1- carboxylic acid [3-(3- cycloheptylureido)propyl] amide B 3.80 379 Ig.10

Octahydroquinoline-1- carboxylic acid {3-[3-(4- thiophen-2- yltetrahydropyran-4- yl)ureido]propyl}amide B 3.47 449 Ie.32

l-cyclohexyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.52 3.62 322 322 Ie.33

1-s-butyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.35 296 Ie.34

1-ethyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 2.78 2.90 268 268 Ie.35

1-isopropyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.01 3.12 282 282 Ie.36

1-furan-2-ylmethyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.15 3.26 320 320 Ie.37

1-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylurea B 4.25 374 Ie.38

1-cycloheptyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.83 336 Ie.39

1-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]-3- phenylurea B 3.60 316 Ie.40

1-benzyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.41 3.50 330 330 Ie.41

1-(4-fluorophenyl)-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.57 3.67 334 334 Ig.11

octahydroisoquinoline-2- carboxylic acid [3-(3- cyclohexylureido)propyl] amide B 3.59 3.68 365 365 Ig.12

Octahydroisoquinoline- 2-carboxylic acid [3-(3- phenylureido)propyl]amide B 3.51 3.60 359 359 Ig.13

Octahydroisoquinoline- 2-carboxylic acid [3-(3- benzylureido)propyl]amide B 3.45 3.54 373 373 Ig.14

Octahydroisoquinoline- 2-caxboxylic acid {3-[3- (4-fluorophenyl)ureido] propyl}amide B 3.57 3.66 377 377 Ig.15

Octahydroisoquinoline- 2-carboxylic acid [3-(3-s- butylureido)propyl]amide B 3.33 3.42 339 339 Ig.16

Octahydroisoquinoline- 2-carboxylic acid [3-(3-t- butylureido)propyl]amide B 3.46 3.56 339 339 Ig.17

Octahydroisoquinoline- 2-carboxylic acid [3-(3- furan-2- ylmethylureido)propyl] amide B 3.22 3.32 363 363 Ig.18

Octahydroisoquinoline- 2-carboxylic acid {3-[3- (6-fluoro-4H-1,3- benzodioxin-8- yl)ureido]propyl}amide B 3.67 3.75 435 435 Ig.19

Octahydroisoquinoline- 2-carboxylic acid [3-(3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylureido)propyl]amide B 4.23 4.31 417 417 Ig.20

Octahydroisoquinoline- 2-carboxylic acid [3-(3- cycloheptylureido)propyl] amide B 3.79 3.88 379 379 Ie.43

1-[3-(octahydroquinolin- 1-yl)-3-oxopropyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylthiourea B 4.68 404 Ie.44

1-benzyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea B 3.88 360 Ie.45

1-cyclopentyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea B 3.84 338 Ie.46

1-(2-cyclohex-1- enylethyl)-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea B 4.40 378 Ie.47

1-cyclohexylmethyl-3- [3-(octahydroquinolin-1- yl)-3-oxopropyl]thiourea A 7.92 366 Ie.48

1-t-butyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea A 7.11 326 Ie.49

1-cyclohexyl-3-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea A 7.47 352 Ie.50

1-[3-(octahydroquinolin- 1-yl)-3-oxopropyl]-3- phenylthiourea A 6.94 346 Ie.51

1-benzhydryl-3-{3- (octahydroquinolin-1-yl)- 3-oxopropyl]thiourea A 8.22 436 Ie.52

1-cyclohexylmethyl-3- [4-(octahydroquinolin-1- yl)-4-oxobutyl]thiourea B 4.33 380 Ie.53

l-cyclohexyl-3-[4- (octahydroquinolin-1-yl) 4-oxobutyl]thiourea B 4.10 366 Ig.21

Octahydroquinoline-1- carboxylic acid [3-(3- cyclohexylmethyl- thioureido)propyl]amide B 4.23 395 Ig.22

Octahydroquinoline-1- carboxylic acid [3-(3-t- butylthioureido)propyl] amide B 3.79 355 Ig.23

Octahydroquinoline-1- carboxylic acid [3-(3- benzylthioureido)propyl] amide B 3.82 389 Ig.24

Octahydroquinoline-1- carboxylic acid [3-(3- cyclopentylthioureido) propyl]amide B 3.79 367 Ig.25

Octahydroquinoline-1- carboxylic acid {3-[3-(2- cyclohex-1- enylethyl)thioureido] propyl}amide B 4.32 407 Ig.26

Octahydroquinoline-1- carboxylic acid [3-(3- phenylthioureido)propyl] amide B 3.66 375 Ig.27

Octahydroquinoline-1- carboxylic acid [3-(3- cyclohexylthioureido) propyl]amide B 4.00 381 Ig.28

Octahydroquinoline-1- carboxylic acid [3-(3- benzhydrylthioureido) propyl]amide B 4.41 465 Ie.54

1-cyclohexylmethyl-3- [5-(octahydroquinolin-1- yl)-5-oxopentyl]thiourea B 4.32 394 Ie.55

1-[5-(octahydroquinolin- 1-yl)-5-oxopentyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylthiourea B 4.67 432 Ie.56

1-t-butyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 3.90 354 Ie.57

1-cyclohexyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 4.10 380 Ie.58

1-benzhydryl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 4.49 464 Ie.59

1-benzyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 3.93 388 Ie.60

1-cyclopentyl-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 3.89 366 Ie.61

1-(2-cyclohex-1- enylethyl)-3-[5- (octahydroquinolin-1-yl)- 5-oxopentyl]thiourea B 4.42 406 Ie.62

1-[5-(octahydroquinolin- 1-yl)-5-oxopentyl]-3- phenylthiourea B 3.81 374 Ie.63

1-cyclohexylmethyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 4.35 4.44 352 352 Ie.64

1-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]-3- tricyclo[3.3.1.1^(3.7)]decan- 1-yl thiourea B 4.77 4.81 390 390 Ie.65

1-t-butyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 3.90 4.01 312 312 Ie.66

1-cyclohexyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 4.10 4.19 338 338 Ie.67

1-benzhydryl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 4.52 4.59 nd nd Ie.68

1-cyclopentyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 3.89 3.99 324 324 Ie.69

1-(2-cyclohex-1- enylethyl)-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]thiourea B 4.45 4.53 364 364 Ig.29

Octahydroisoquinoline- 2-carboxylic acid [3-(3- cyclohexylmethyl- thioureido)propyl]amide B 4.22 4.30 395 395 Ig.30

Octahydroisoquinoline- 2-carboxylic acid [3-(3- tricyclo[3.3.1.1^(3.7)]decan- 1-ylthioureido)propyl] amide B 4.65 4.71 433 433 Ig.31

Octahydroisoquinoline- 2-carboxylic acid [3-(3-t- butylthioureido)propyl] amide B 3.78 3.87 355 355 Ig.32

Octahydroisoquinoline- 2-carboxylic acid [3-(3- benzylthioureido)propyl] amide B 3.81 3.89 389 389 Ig.33

Octahydroisoquinoline- 2-carboxylic acid [3-(3- cyclopentylthioureido) propyl]amide B 3.78 3.87 367 367 Ig.34

Octahydroisoquinoline- 2-carboxylic acid {3-[3- (2-cyclohex-1- enylethyl)thioureido] propyl}amide B 4.31 4.39 407 407 Ig.35

Octahydroisoquinoline- 2-carboxylic acid{3-[3- (4-thiophen-2- yltetrahydropyran-4- yl)ureido]propyl}amide B 3.45 3.54 449 449 Ie.70

1-[4-(octahydroquinolin- 1-yl)-4-oxobutyl]-3-[4- (thiophen-2- yl)tetrahydropyran-4- yl]urea B 3.43 434 Ie.71

Octahydroquinoline-1- carboxylic acid N-[3- (octahydroquinolin-1-yl)- 3-oxopropyl]amide B 4.09 376 Ie.72

1-[(3s,5s,7s)-adamantan- 1-yl]-3-[3- (octahydroisoquinolin-2- yl)-3-oxopropyl]urea B 4.17 4.26 388 388 Ie.73

1-isopropyl-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]urea B 4.60 4.68 324 324 Ie.74

1-[(3s,5s,7s)-adamantan- 1-yl]-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]urea B 4.27 4.35 416 416 Ie.75

1-t-butyl-3-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]urea B 3.47 296 Ie.76

1-[2- (octahydroisoquinolin-2- yl)-2-oxoethyl]-3- (thiophen-2-yl)urea B 3.50 322 Ie.77

1-[(3s,5s,7s)-adamantan- 1-yl]-3-[4- (octahydroquinolin-1-yl)- 4-oxobutyl]thiourea B 4.68 418 Ie.78

1-[2-(cyclohex-1-en-1- yl)ethyl]-3-[4- (octahydroquinolin-1-yl)- 4-oxobutyl]thiourea B 4.44 392 Ie.79

1-[(3s.,5s.7s)-adamantan- 1-yl]-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 4.67 4.74 432 432 Ie.80

1-cyclopentyl-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 3.88 3.98 366 366 Ie.81

3-phenyl-1-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]-thiourea B 3.81 3.87 374 374 Ie.82

1-(cyclohexylmethyl)-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 4.32 4.40 394 394 Ie.83

1-t-butyl-3-[5- (octahydroisoquinolin-2- yl)-5-oxopenty]thiourea B 3.89 3.99 354 354 Ie.84

1-cyclohexyl-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 4.09 4.18 380 380 Ie.85

1-benzhydryl-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 4.49 4.56 464 464 Ie.86

1-[2-(cyclohex-1-en-1 yl)ethyl]-3-[5- (octahydroisoquinolin-2- yl)-5-oxopentyl]thiourea B 4.41 4.49 406 406 Ig.36

Octahydroquinoline-1- carboxylic acid N-[3-(3- ethylureido)propyl]amide B 2.91 311 Ie.37

Octahydroquinoline-1- carboxylic acid N-[3-(3- isopropylureido)propyl] amide B 3.13 325 Ig.38

Octahydroquinoline-1- carboxylic acid N-[3-[3- (6-fluoro-4H- benzo[d][1,3]dioxin-8- yl)ureido]propyl]amide B 3.69 435 Ig .39

Octahydroquinoline-1- carboxylic acid N-[3-[3- thiophen-2- yl)ureido]propyl]amide B 3.34 365 Ig.40

Octahydroisoquinoline- 2-carboxylic acid N-[3- (3-ethylureido)propyl] amide B 3.02 311 Ig.41

Octahydroisoquinoline- 2-carboxylic acid N-[3- (3-isopropylureido)propyl] amide B 3.23 325 Ig.42

Octahydroisoquinoline- 2-carboxylic acid N-[3- [3-(thiophen-2- yl)ureido]propyl]amide B 3.51 365 Ig.43

Octahydroquinoline-1- carboxylic acid N-[3-[3- [(3s,5s,7s)-adamantan-1- yl]thioureido]propyl] amide B 4.67 433

Example Id.1 N-[3-(octahydroquinolin-1-yl)-3-oxopropyl]-2-thiophen-2-ylacetamide

46 μL of Et₃N, 30.4 mg (0.22 mmol) of HOBT and 43.1 mg (0.22 mmol) of EDC are added to a solution of 21.3 mg (0.15 mmol) of 2-thienylacetic acid in 2 mL of AcOEt; 35 mg (0.17 mmol) of the intermediate amine Vc.3 are added to it. The suspension formed is kept under stirring for 18 h. It is then treated with water and more AcOEt is added, the organic phase is separated and the aqueous phase is extracted once more with more AcOEt. The organic phases are pooled and successively washed with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The residue is purified by means of silica gel column chromatography, using a (30:1) mixture of DCM-MeOH as eluent, yielding 5 mg of an oil identified as example Id.1. Method A: tr: 6.30 min; m/z: 335.

Example Id.2 N-[3-(octahydroquinolin-1-yl)-3-oxopropyl]propionamide

35 mg (0.17 mmol) of the intermediate amine Vc.3 and 46 μL of Et₃N are added to a solution of 13 μL (0.15 mmol) of propionyl chloride in 2 mL of AcOEt. The solution formed is kept under stirring for 18 h. It is then treated with water and more AcOEt is added, the organic phase is separated and the aqueous phase is extracted once more with more AcOEt. The organic phases are pooled and successively washed with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure, 11 mg of example Id.2 being obtained. Method A: tr: 5.35 min; m/z: 267.

The following examples were prepared in a manner similar to examples 1d.1 or Id.2:

Ex. structure name method tr (min) m/z Id.3 

1-methyl-1H-indole-2- carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.41 368 Id.4 

3-cyclohexyl-N-[3- (octahydroquinolin-1-yl)-3- oxopropyl]propionamide A 7.70 349 Id.5 

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-3- phenylpropionamide A 6.71 343 Id.6 

Isoquinoline-3-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.05 366 Id.7 

2-naphthalen-2-yl-N-[3- (octahydroquinolin-1-yl)-3- oxopropyl]acetamide A 7.16 379 Id.8 

Benzofuran-2-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.03 355 Id.9 

Isoquinoline-1-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.11 366 Id.10

Quinoline-4-carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 5.65 366 Id.11

Quinoline-3-carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 6.00 366 Id.12

Quinoline-2-carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.29 366 Id.13

Isoquinoline-5-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 4.68 366 Id.14

1-phenylcyclopentanecarboxylic acid [3-(octahydroquinolin-1- yl)-3-oxopropyl]amide A 7.87 383 Id.15

1-phenylcyclohexanecarboxylic acid [3-(octahydroquinolin-1- yl)-3-oxopropyl]amide A 8.21 397 Id.16

4,4- difluorocyclohexanecarboxylic acid [3-(octahydroquinolin-1- yl)-3-oxopropyl]amide A 6.49 357 Id.17

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-2- phenylacetamide A 6.42 329 Id.18

Cyclopentanecarboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 6.39 307 Id.19

Cyclohexanecarboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 6.76 321 Id.20

Furan-2-carboxylic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 5.89 305 Id.21

3-cyclopentyl-N-[3- (octahydroquinolin-1-yl)-3- oxopropyl]propionamide A 7.28 335 Id.22

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]benzamide A 6.39 315 Id.23

(E)-N-[3-(octahydroquinolin-1- yl)-3-oxopropyl]-3- phenylacrylamide A 6.77 341 Id.24

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-4- phenylbutyramide A 7.05 357 Id.25

2-(1-methyl-1H-indol-3-yl)-N- [3-(octahydroquinolin-1-yl)-3- oxopropyl]acetamide A 6.83 382 Id.26

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-2-thiophen-3- ylacetamide A 6.27 335 Id.27

Thiophene-2-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 6.26 321 Id.28

Naphthalene-1-carboxylic acid [3-(octahydroquinolin-1-yl)-3- oxopropyl]amide A 7.09 365 Id.29

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]butyramide A 5.79 281 Id.30

N-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]benzamide A 6.43 329 Id.31

(E)-N-[4-(octahydroquinolin-1- yl)-4-oxobutyl]-3- phenylacrylamide A 6.75 355 Id.32

N-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]-4- phenylbutyramide A 7.03 371 Id.33

N-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]-2-phenylacetamide A 6.44 343 Id.34

Thiophene-2-carboxylic acid [4-(octahydroquinolin-1-yl)-4- oxobutyl]amide A 6.32 335 Id.35

Naphthalene-1-carboxylic acid [4-(octahydroquinolin-1-yl)-4- oxobutyl]amide A 7.04 379 Id.36

Cyclohexanecarboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide A 6.77 335 Id.37

Furan-2-carboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide A 5.87 319 Id.38

3-cyclopentyl-N-[4- (octahydroquinolin-1-yl)-4- oxobutyl]propionamide A 7.27 349 Id.39

2-cyclohexyl-N-[4- (octahydroquinolin-1-yl)-4- oxobutyl]acetamide A 7.14 349 Id.40

1-(3-fluorophenyl) cyclopentanecarboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide A 7.95 415 Id.41

1-phenylcyclopentanecarboxylic acid [4-(octahydroquinolin-1- yl)-4-oxobutyl]amide A 7.83 397 Id.42

1-phenylcyclopropanecarboxylic acid [4-(octahydroquinolin-1- yl)-4-oxobutyl]amide A 7.23 369 Id.43

1-phenylcyclohexanecarboxylic acid [4-(octahydroquinolin-1- yl)-4-oxobutyl]amide A 8.16 411 Id.44

1-(4-chlorophenyl) cyclobutanecarboxylic acid [4- (octahydroquinolin-1-yl)-4- oxobutyl]amide A 7.94 417 Id.45

2-cyclopentyl-N-[4- (octahydroquinolin-1-yl)-4- oxobutyl]acetamide A 6.77 335 Id.46

Cyclohexanecarboxylic acid [3- (octahydroisoquinolin-2-yl)-3- oxopropyl]amide A 6.74 6.93 321 321 Id.47

3-cyclopentyl-N-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]propionamide A 7.27 7.44 335 335 Id.48

1-(4-chlorophenyl) cyclobutanecarboxylic acid [3- (octahydroisoquinolin-2-yl)-3- oxopropyl]amide A 7.95 8.09  403, 405  403, 405 Id.49

N-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]benzamide A 6.34 6.53 315 315 Id.50

(E)-N-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]-3-phenylacrylamide A 6.71 6.88 341 341 Id.51

N-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]-4- phenylbutyramide A 7.02 7.19 357 357 Id.52

N-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]-2- phenylacetamide A 6.41 6.59 329 329 Id.53

Cyclopentanecarboxylic acid [3-(octahydroisoquinolin-2-yl)- 3-oxopropyl]amide A 6.38 6.57 307 307 Id.54

Naphthalene-1-carboxylic acid [3-(octahydroisoquinolin-2-yl)- 3-oxopropyl]amide A 7.04 7.21 365 365 Id.55

Furan-2-carboxylic acid [3- (octahydroisoquinolin-2-yl)-3- oxopropyl]amide A 5.84 6.05 305 305 Id.56

2-cyclohexyl-N-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]acetamide A 7.14 7.30 335 335 Id.57

3-cyclohexyl-N-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]propionamide A 7.67 7.83 349 349 Id.58

1-(3-fluorophenyl) cyclopentanecarboxylic acid [3- (octahydroisoquinolin-2-yl)-3- oxopropyl]amide A 7.95 8.09 401 401 Id.59

1-phenylcyclopentanecarboxylic acid [3-(octahydroisoquinolin- 2-yl)-3-oxopropyl]amide A 7.84 7.99 383 383 Id.60

1-phenylcyclopropanecarboxylic acid [3-(octahydroisoquinolin- 2-yl)-3-oxopropyl]amide A 7.25 7.41 355 355 Id.61

1-phenylcyclohexanecarboxylic acid [3-(octahydroisoquinolin- 2-yl)-3-oxopropyl]amide A 8.17 8.31 397 397 Id.62

Thiophene-2-carboxylic acid [3-(octahydroisoquinolin-2-yl)- 3-oxopropyl]amide A 6.21 6.39 321 321

Example It.1 N-[3-(octahydroquinolin-1-yl)-3-oxopropyl]propionamide

23.4 mg (0.11 mmol) of the intermediate amine Vc.6 and 29 μL of Et₃N are added to a solution of 18.1 mg (0.10 mmol) of benzenesulfonyl chloride in 2 mL of AcOEt. The solution formed is kept under stirring at rt for 18 h. It is then treated with water and more AcOEt is added, the organic phase is separated and the aqueous phase is extracted once more with more AcOEt. The organic phases are pooled and successively washed with saturated NaHCO₃ solution, 1N HCl and brine. It is then dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The residue is purified by means of silica gel column chromatography, using a (1:1) mixture of hexane-AcOEt as eluent, yielding 23 mg of a yellowish paste identified as example It.1. Method A: tr: 6.76 min/6.97 min; m/z: 351/351

The following examples were prepared in a manner similar to example 1t.1:

Ex. structure name method tr (min) m/z It.2

N-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]-C- phenylmethanesulfonamide A 6.84 379 It.3

N-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]benzosulfonamide A 6.79 365 It.4

Propane-1-sulfonic acid [3- (octahydroquinolin-1-yl)-3- oxopropyl]amide A 6.26 317 It.5

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]benzesulfonamide A 6.82 351 It.6

N-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-C- phenylmethanesulfonamide A 6.85 365 It.7

N-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]-C- phenylmethanesulfonamide A 6.84 7.01 365 365

Example Ip.1 Cycloheptylthiocarbamic acid S-[4-(octahydroisoquinolin-2-yl)-4-oxobutyl]ester

12.8 μL of cycloheptylisocyanate (0.1 mmol) are added to a solution of 35 mg (0.15 mmol) of intermediate IVp.4 and 23 μL of Et₃N in 2 mL of THF at 0° C. Once added it is left to stir at reflux for 24 h. AcOEt is then added to the reaction mixture and it is sequentially washed with water and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The residue is purified by means of silica gel column chromatography, using a (200:3) mixture of DCM-MeOH as eluent, yielding 23 mg of a colorless paste identified as example Ip.1. Method B: tr: 4.63 min; m/z: 381

The following compounds were prepared in a manner similar to example Ip.1:

Ex. structure name method tr (min) m/z Ip.2 

Cyclohexylthiocarbamic acid S-[4- (octahydroquinolin-1-yl)-4- oxobutyl] ester B 4.34 367 Ip.3 

Phenylthiocarbamic acid S-[4- (octahydroquinolin-1-yl)-4- oxobutyl] ester B 4.14 361 Ip.4 

(4-fluorophenyl)thiocarbamic acid S-[4-(octahydroquinolin-1-yl)-4- oxobutyl] ester B 4.19 379 Ip.5 

Benzylthiocarbamic acid S-[4- (octahydroquinolin-1-yl)-4- oxobutyl] ester B 4.08 375 Ip.6 

(2-cyclohex-1- enylethyl)dithiocarbamic acid 4- (octahydroisoquinolin-2-yl)-4- oxobutyl ester B 5.19 409 Ip.7 

(Furan-2-ylmethyl)carbamic acid S-[4-(octahydroquinolin-1-yl)-4- oxobutyl] ester B 3.82 365 Ip.8 

Cycloheptylthiocarbamic acid S- [4-(octahydroquinolin-1-yl)-4- oxobutyl] ester B 4.54 381 Ip.9 

Octahydroquinoline-1- thiocarbamic acid S-[3- (octahydroquinolin-1-yl)-3- oxopropyl] ester B 4.94 393 Ip.10

Benzyldithiocarbamic acid 4- (octahydroquinolin-1-yl)-4- oxobutyl ester B 4.54 391 Ip.11

[2-(cyclohex-1-en-1- yl)ethyl]dithiocarbamic acid 4- (octahydroquinolin-1-yl)-4- oxobutyl ester B 5.13 409 Ip.12

Cyclohexyldithiocarbamic acid 4- (octahydroquinolin-1-yl)-4- oxobutyl ester B 4.82 383 Ip.13

Benzhydryldithiocarbamic acid 4- (octahydroquinolin-1-yl)-4- oxobutyl ester B 4.98 467 Ip.14

Octahydroquinoline-1- thiocarbamic acid S-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl] ester B 4.93 5.02 393 393 Ip.15

Cyclohexyldithiocarbamic acid 4- (octahydroisoquinolin-2-yl)-4- oxobutyl ester B 4.83 4.89 383 383

Example Ik.1 1-[2-(octahydroquinolin-1-yl)-2-oxoethyl]-3,4-diphenylpyrrole-2,5-dione

22 mg of the intermediate amine Vc.2 (0.11 mmol) are added to a solution of 34 mg (0.13 mmol) of 3,4-diphenylfuran-2,5-dione in 2 mL of DMF. Once added it is left to stir at 100° C. for 48 h. AcOEt is then added to the reaction mixture and it is sequentially washed with water, 5% NaHCO₃ solution and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The residue is purified by means of silica gel column chromatography, using a (3:2) mixture of hexane-AcOEt as eluent, yielding 7.5 mg of a paste identified as example Ik.1. Method A: tr: 8.55 min; m/z; 429

The following compounds were prepared in a manner similar to example Ik.1:

Ex. structure name method tr (min) m/z Ik.2 

5,6-dichloro-2-[2- (octahydroquinolin-1-yl)-2- oxoethyl]isoindole-1,3-dione A 8.12  395,  397, 399 Ik.3 

(2R,6S)-4-[2- (octahydroquinolin-1-yl)-2- oxoethyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 6.85 357 Ik.4 

5-fluoro-2-[2- (octahydroquinolin-1-yl)-2- oxoethyl]isoindole-1,3-dione A 7.16 345 Ik.5 

4-fluoro-2-[2- (octahydroquinolin-1-yl)-2- oxoethyl]isoindole-1,3-dione A 7.03 345 Ik.6 

(3aR,7aS)-2-[2- (octahydroquinolin-1-yl)-2- oxoethyl]hexahydroisoindole- 1,3-dione A 6.76 333 Ik.7 

(3aS,7aR)-2-[3- (octahydroquinolin-1-yl)-3- oxopropyl]hexahydroisoindole- 1,3-dione A 6.89 347 Ik.8 

(2R,6S)-4-[3- (octahydroquinolin-1-yl)-3- oxopropyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.07 371 Ik.9 

(3aS,7aS)-2-[3- (octahydroquinolin-1-yl)-3- oxopropyl]hexahydroisoindole- 1,3-dione A 6.89 347 Ik.10

4-hydroxy-2-[3- (octahydroquinolin-1-yl)-3- oxopropyl]isoindole-1,3-dione A 6.28 357 Ik.11

5-fluoro-2-[3- (octahydroquinolin-1-yl)-3- oxopropyl]isoindole-1,3-dione A 7.25 359 Ik.12

5,6-dichloro-2-[3- (octahydroquinolin-1-yl)-3- oxopropyl]isoindole-1,3-dione A 8.27  409,  411, 413 Ik.13

1-[3-(octahydroquinolin-1-yl)- 3-oxopropyl]-3,4- diphenylpyrrole-2,5-dione A 8.62 443 Ik.14

5,6-dichloro-2-[4- (octahydroquinolin-1-yl)-4- oxobutyl]isoindole-1,3-dione A 8.43  423,  425, 427 Ik.15

1-[4-(octahydroquinolin-1-yl)- 4-oxobutyl]-3,4- diphenylpyrrole-2,5-dione A 8.75 457 Ik.16

(3aR,7aR)-2-[4- (octahydroquinolin-1-yl)-4- oxobutyl]hexahydroisoindole- 1,3-dione A 7.04 361 Ik.17

(2R,6S)-4-[4- (octahydroquinolin-1-yl)-4- oxobutyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.14 385 Ik.18

5-fluoro-2-[4- octahydroquinolin-1-yl)-4- oxobutyl]isoindole-1,3-dione A 7.38 373 Ik.19

4-fluoro-2-[4- (octahydroquinolin-1-yl)-4- oxobutyl]isoindole-1,3-dione A 7.19 373 Ik.20

(3aR,7aS)-2-[4- (octahydroquinolin-1-yl)-4- oxobutyl]hexahydroisoindole- 1,3-dione A 7.13 361 Ik.21

4-hydroxy-2-[5- (octahydroquinolin-1-yl)-5- oxopentyl]isoindole-1,3-dione A 6.64 6.69 385 385 Ik.22

(2R,65)-4-[5- (octahydroquinolin-1-yl)-5- oxopentyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.32 399 Ik.23

5,6-dichloro-2-[5- (octahydroquinolin-1-yl)-5- oxopentyl]isoindole-1,3-dione A 8.62  437,  439, 441 Ik.24

(3aS,7aR)-2-[5- (octahydroquinolin-1-yl)-5- oxopentyl]hexahydroisoindole- 1,3-dione A 7.22 375 Ik.25

5-fluoro-2-[5- (octahydroquinolin-1-yl)-5- oxopentyl]isoindole-1,3-dione A 7.61 387 Ik.26

1-[5-(octahydroquinolin-yl)-1- yl)-5-oxopentyl]-3,4- diphenylpyrrole-2,5-dione A 8.90 471 Ik.27

5,6-dichloro-2-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]isoindole-1,3-dione A 8.24  395,  397, 399 Ik.28

4-hydroxy-2-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]isoindole-1,3-dione A 6.45 343 Ik.29

(2R,6S)-4-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.02 357 Ik.30

5-fluoro-2-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]isoindole-1,3-dione A 7.14 7.31 345 345 Ik.31

4-fluoro-2-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]isoindole-1,3-dione A 7.19 345 Ik.32

(3aR,7aS)-2-[2- (octahydroisoquinolin-2-yl)-2- oxoethyl]hexahydroisoindole- 1,3-dione A 6.76 6.94 333 333 Ik.33

1-[3-(octahydroisoquinolin-2- yl)-3-oxopropyl]-3,4- diphenylpyrrole-2,5-dione A 8.61 8.73 443 443 Ik.34

(3aR,7aR)-2-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]hexahydroisoindole- 1,3-dione A 6.89 7.07 347 347 Ik.35

5-fluoro-2-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]isoindole-1,3-dione A 7.36 359 Ik.36

4-fluoro-2-[3- (octahydroisoquinolin-2-yl)-3- oxopropyl]isoindole-1,3-dione A 7.01 7.18 359 359 Ik.37

4-hydroxy-2-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]isoindole-1,3-dione A 6.45 6.61 371 371 Ik.38

(2R,6S)-4-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.14 7.32 385 385 Ik.39

5,6-dichloro-2-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]isoindole-1,3-dione A 8.43 8.56  423,  425, 427  423,  425, 427 Ik.40

1-[4-(octahydroisoquinolin-2- yl)-4-oxobutyl]-3,4- diphenylpyrrole-2,5-dione A 8.77 8.89 457 457 Ik.41

(3aS,7aR)-2-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]hexahydroisoindole- 1,3-dione A 7.04 7.22 361 361 Ik.42

5-fluoro-2-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]isoindole-1,3-dione A 7.39 7.55 373 373 Ik.43

4-fluoro-2-[4- (octahydroisoquinolin-2-yl)-4- oxobutyl]isoindole-1,3-dione A 7.20 7.36 373 373 Ik.44

4-hydroxy-2-[5- (octahydroisoquinolin-2-yl)-5- oxopentyl]isoindole-1,3-dione A 6.64 6.80 385 385 Ik.45

(2R,6S)-4-[5- (octahydroisoquinolin-2-yl)-5- oxopentyl]-4- azatricyclo[5.2.2.0^((2,6))]undec-8- ene-3,5-dione A 7.50 399 Ik.46

5-fluoro-2-[5- (octahydroisoquinolin-2-yl)-5- oxopentyl]isoindole-1,3-dione A 7.59 7.75 387 387 Ik.47

5,6-dichloro-2-[5- (octahydroisoquinolin-2-yl)-5- oxopentyl]isoindole-1,3-dione A 8.60 8.72  437,  439, 441  437,  439, 441

Example Ij.1 [3-(octahydroquinolin-1-yl)-3-oxopropyl]carbamic acid t-butylester

0.12 mg (1 μmol) of 4-dimethylaminopyridine and 43 mg (0.2 mmol) of di-tertbutyl dicarbonate are added to a solution of 21 mg (0.1 mmol) of intermediate Vc.3 in 2 mL of DCM. The mixture is stirred for 18 h at rt. The solvent is evaporated and water and AcOEt are then added, the aqueous phase is separated and extracted again with AcOEt, the pooled organic phases are sequentially washed with 1N HCl and brine. The organic phase is dried over anhydrous Na₂SO₄, it is filtered and the solvent is evaporated under reduced pressure. The residue is purified by means of silica gel column chromatography, using a (20:1) mixture of DCM-MeOH as eluent, yielding 6.5 mg of a colorless paste identified as example Ij.1. Method A: tr: 7.15 min; m/z: 311

Pharmacological Examples Determination of the Inhibitory Activity of 11-Beta-HSD1 in the Microsomal Fraction of Transfected HEK293 Cells

99 μL of a reaction mixture which contained 80 nM [³H]-cortisone, 1 mM NADPH and 40 μg/mL of the microsome preparations of HEK-293 cells stably transfected with the 11-beta-HSD1 clone, dissolved in assay buffer (50 mM HEPES, 100 mM KCl, 5 mM NaCl, 2 mM MgCl₂/100 mL H₂O) were added to a 96-well plate. The inhibitors to be analyzed were dissolved in 100% DMSO, and the final concentration in the reaction was 1%.

The reaction mixture was incubated for 2 hours at 37° C. under stirring. The total reaction volume per well was 100 μL. The stop solution (5 mg/mL ProteinA Spa bead, Superblock Blocking Buffer, 30 μM glycyrrhetinic acid, 1 μg/mL anticortisol monoclonal antibody) was simultaneously prepared, being incubated under stirring for two hours at rt and protected from light. Once the two hours lapsed, 50 μL of the stop solution were dispensed to each well in the reaction plate and was left to incubate for two hours at rt under stirring and protected from light. Once the second incubation ended, the plate was read in a 1450 Microbeta Tritalux (Wallac®) scintillation counter for 30 seconds per well.

Determination of the Inhibitory Activity of 11-Beta-HSD2 in the Microsomal Fraction of Transfected HEK293 Cells

59 μL of the reaction mixture were added to a 96-well plate. This contained 1 mM NAD⁺ and 80 μg/mL of the microsome preparations of HEK-293 cells stably transfected with the 11-beta-HSD2 clone, dissolved in assay buffer (50 mM HEPES, 100 mM KCl, 5 mM NaCl, 2 mM MgCl₂/100 mL H₂O). The inhibitors to be analyzed were dissolved in 100% DMSO, and the final concentration in the reaction was 1%. The reaction mixture was pre-incubated for 30 minutes at 37° C. under stirring. 40 μL of the reaction substrate, 3.2 nM [³H]-cortisol dissolved in assay buffer were added. It was incubated at 37° C. for two hours under stirring. The stop solution was simultaneously prepared, being incubated for two hours at rt and protected from light. After this time 50 μL of the stop solution were added to end the reaction, and it was incubated for two hours at rt under stirring and protected from light. The signal emitted by SPA heads-cortisol complex was measured in the 1450 Microbeta Tritalux (Wallac®) scintillation counter for 30 seconds per well. This case measures the binding to the substrate, and not to the product as in the assay for the type 1 isoenzyme.

The following table indicates the activity values of some compounds described in the examples expressed as percentage of inhibition at a 10 μM concentration.

% Inhibition (10 μM) Example 11-beta-HSD1 11-beta-HSD2 Ia.59 100 0 Ia.61 93 0 Ia.66 100 6 Ib.8 100 5 Ib.18 100 10 Ib.80 100 13 Ie.16 100 5 Ib.8 100 0 Id.6 100 0 Id.12 100 0 If.1 100 0 Ik.25 100 6 If.8 100 4 

The invention claimed is:
 1. A compound of formula (I)

and pharmaceutically acceptable salts thereof, wherein: s and p are an integer selected in an opposite manner between 0 and 1, such that when s is 1, p is 0 (to form a perhydroquinoline) and when s is 0, p is 1 (to form a perhydroisoquinoline), Y is a biradical selected from CO, CS and SO2, W1 and W2 is each independently a bond or a biradical selected from O, S and NR1, wherein R1 is selected from H, C1-4 alkyl and C3-10 cycloalkyl, n is an integer selected from 0, 1, 2, 3 and 4, V is a radical selected from the group consisting of —CO-T, —CS-T and —SO2-T, or a radical selected from the group consisting of:

where T is a group selected from the group consisting of NR2R3, R2, OR2 and SR2; or a group selected from the group

consisting of: wherein R2 and R3 is each independently H, COR4, SO2R4, C1-4 alkyl, aryl, benzyl, phenethyl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl or a saturated, partially unsaturated or aromatic, 5 to 10 membered heterocycle, containing one or several heteratoms elected from the group consisting of nitrogen, oxygen and sulfur, wherein when R2 or R3 is an alkyl, or an alkenyl these can be optionally substituted with one or several substituents independently selected from the group consisting of F, OR4, NR4R5, COOR4, CONR4R5, C3-10 cycloalkyl, aryl and heterocycle; and wherein when R2 or R3 is an aryl, a benzyl, a phenethyl, a cycloalkyl or a heterocycle, these can be optionally substituted with one or several substituents independently selected from the group consisting of NH2, F, Cl, CN, NO2, COOH, R4, COOR4, OR4, OCF3, SH, SR4, CONR4R5, SO2NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO2R4 and heterocycle; and wherein when R2 or R3 is a cycloalkyl, this can be optionally substituted with one or several fused benzene rings, the benzene could be optionally substituted with one or several substituents independently selected from the group consisting of alkyl, alkoxide and halogen, wherein R4 and R5 is each independently selected from the group consisting of H, C1-4 alkyl, aryl, benzyl, phenethyl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl and heterocycle, or optionally R4 and R5 can be bound to one another forming a 3 to 8 membered cycle, wherein R6, R7, R8 and R9 is each independently selected from the group consisting of H, OR4, F and Cl, and wherein R10 is independently selected from the group consisting of H, OH, F, C1-4 alkyl, COOR11, COR11, phenyl, benzyl, benzhydryl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl and heterocycle, and wherein the alkyl, phenyl, benzyl, benzhydryl, cycloalkyl or heterocycle can be optionally substituted with one or several substituents independently selected from the group consisting of NH2, F, Cl, NO2, COOH, COOR4, OR4, CF3, SH, SR4, CONR4R5, SO2NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO2R4 and C1-4 alkyl; and where R11 is selected from H, C1-4 alkyl and C3-10 cycloalkyl.
 2. The compound according to claim 1, wherein Y is CO or SO2.
 3. The compound according to claim 1, wherein W1 and W2 is each independently selected from the group consisting of a bond, S and NR1.
 4. The compound according to claim 3, wherein R1 is H.
 5. The compound according to claim 1, wherein V is —CO-T, —CS-T or -SO2-T.
 6. The compound according to claim 1, wherein V is selected from the group consisting of:


7. The compound according to claim 1, wherein T is NR2R3, R2, OR2 or SR2.
 8. The compound according to claim 1, wherein R2 and R3 is each independently selected from the group consisting of H, COR4, SO2R4, C1-4 alkyl, phenyl, naphthyl, benzyl, phenethyl, C2-4 alkenyl, C3-10 cycloalkyl, and heterocycle, particularly, 2-furanyl, 2-thiophenyl, 2-(1-methylindole), quinoline, isoquinoline and 2-benzofuranyl.
 9. The compound according to claim 8, wherein R2 and R3 is each independently selected from the group consisting of C1-4 alkyl and C2-4 alkenyl.
 10. The compound according to claim 9, wherein R2 or R3 are optionally substituted with one or several substituents independently selected from the group consisting of F, OR4, NR4R5, COOR4, CONR4R5, phenyl, C3-10 cycloalkyl, hexenyl, naphthyl and heterocycle, particularly pyridine, 3-(1-methylindole), 3-thiophenyl and 2-furanyl.
 11. The compound according to claim 8, wherein R2 and R3 is each independently selected from the group consisting of phenyl, benzyl, phenethyl and C3-10 cycloalkyl.
 12. The compound according to claim 11, wherein R2 or R3 are optionally substituted with one or several substituents independently selected from the group consisting of F, Cl and OR4.
 13. The compound according to claim 1, wherein R4 and R5 is each independently selected from the group consisting of C1--4 alkyl, benzyl, phenethyl and phenyl.
 14. The compound according to claim 1, wherein T is selected from the group consisting of:


15. The compound according to claim 1, wherein R6, R7, R8 and R9 is each independently selected from H, OR4, F and Cl, and wherein R10 is independently selected from the group consisting of H, OH, F, C1-4 alkyl, COOR11, COR11, phenyl, benzyl and benzhydryl.
 16. The compound according to claim 15, wherein R10 is phenyl, benzyl or benzhydryl.
 17. The compound according to claim 16, wherein R10 is optionally substituted with one or several substituents, independently selected from the group consisting of F, OR4, CF3, COR4 and C1-4 alkyl.
 18. The compound according to claim 1, wherein R11 is H or C3-10 cycloalkyl.
 19. The compound according to claim 1, wherein s is 0 and p is
 1. 20. The compound according to claim 1, wherein s is 1 and p is
 0. 